The Experts below are selected from a list of 2106 Experts worldwide ranked by ideXlab platform
David G Bostwick - One of the best experts on this subject based on the ideXlab platform.
-
Atypical Adenomatous Hyperplasia adenosis of the prostate dna ploidy analysis and immunophenotype
International Journal of Surgical Pathology, 2005Co-Authors: Antonio Lopezbeltran, Junqi Qian, Rodolfo Montironi, Rafael J Luque, David G BostwickAbstract:Atypical Adenomatous Hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular Hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34β-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feul gen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular Hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular Hyperplasia and AAH (p<0.001) and carci...
-
Atypical Adenomatous Hyperplasia of the prostate a premalignant lesion
Cancer Research, 1998Co-Authors: Liang Cheng, Junqi Qian, Ailin Shan, John C Cheville, David G BostwickAbstract:Abstract To better understand genetic alterations in Atypical Adenomatous Hyperplasia (AAH) of the prostate, we examined the prevalence of allelic imbalance at 5 microsatellite polymorphic markers on chromosomes 7q31–35, 8p12–21, 8p22, 8q22.2, and 18q12.2 from 15 patients with AAH. DNA samples were obtained from formalin-fixed paraffin-embedded sections using tissue microdissection. We found allelic imbalance in 7 of 15 (47%) cases of AAH. Genetic changes that commonly occur in early prostatic carcinogenesis and prostate carcinoma are found in AAH. Current data provide evidence of a genetic link between some cases of AAH and carcinoma.
-
relationship between Atypical Adenomatous Hyperplasia aah prostatic intraepithelial neoplasia pin and prostatic adenocarcinoma
Pathologica, 1997Co-Authors: B Helpap, H Bonkhoff, A Cockett, R Montironi, Patricia Troncoso, D Waters, David G BostwickAbstract:: Two histopathologic lesions are considered putative precursors of prostate cancer, but the supportive evidence for one (prostatic intraepithelial neoplasia, or PIN) is much greater than the other (Atypical Adenomatous Hyperplasia, or AAH). High grade PIN is the most likely precursor of carcinoma, arising in the peripheral zone, but probably does not account for well-differentiated cancer arising in the transition zone. The biological significance of Atypical Adenomatous Hyperplasia of the prostate (AAH) is inconclusive at the time. The histological and cytological features of AAH are intermediate between BPH and low grade carcinoma, suggesting that AAH may be a precursor of well differentiated transition; zone carcinoma. In the recent time new findings on morphogenetic aspects of normal and abnormal prostatic growth i.e. stem cell models are discussed and topics about grading and proliferative activities, frequency and histological changes associated with aging as well as clinical relevance of PIN and AAH. This paper reviews the results and discussion at the second international consultation meeting on PIN in Mayo Clinic, Rochester, Nov. 3-4 th. 1995, following the first international consultation meeting of AAH and PIN and origin of the prostatic carcinoma in Ancona, Sept. 11-12 th 1994.
-
chromosomal anomalies in Atypical Adenomatous Hyperplasia and carcinoma of the prostate using fluorescence in situ hybridization
Urology, 1995Co-Authors: Junqi Qian, Robert B Jenkins, David G BostwickAbstract:OBJECTIVES: The genetic alterations of Atypical Adenomatous Hyperplasia (AAH) of the prostate, a possible precursor of prostate adenocarcinoma, have not been previously investigated. METHODS: We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate chromosomal anomalies in Atypical Adenomatous Hyperplasia (23 foci) and adenocarcinoma (31 foci) in 19 whole-mount radical prostatectomy specimens. RESULTS: Chromosomal anomalies were found in 2 foci (9%) of AAH and 17 foci (55%) of carcinoma. There was no relationship between the chromosomal anomalies in AAH and matched foci of carcinoma. CONCLUSIONS: These findings indicate that AAH is not obviously linked genetically to prostate cancer, although it occasionally contains chromosomal anomalies.
-
mucin expression in Atypical Adenomatous Hyperplasia of the prostate
Human Pathology, 1995Co-Authors: Junqi Qian, David G Bostwick, Neal S GoldsteinAbstract:Abstract Prostatic Atypical Adenomatous Hyperplasia (AAH) is a small glandular proliferation that has histological similarities with well-differentiated adenocarcinoma. To determine the histochemical profile of AAH, we assessed the production of total neutral mucin, total acidic mucin, and sulfated acidic mucin in 24 cases of AAH, five cases of Gleason primary pattern 1 and 2 adenocarcinoma, and 29 cases of adjacent benign and hyperplastic prostatic tissue. All specimens were formalin-fixed transurethral resections, and the diagnosis in each was confirmed by evaluation of the keratin 34B-E12 immunoreactive basal cell layer (intact in benign and hyperplastic epithelium, fragmented in AAH, and absent in cancer). The extent of mucin staining was measured semiquantitatively in 10% increments according to the number of stained glands. Neutral mucin was found in all but two cases, and there was no apparent difference in the amount of staining in benign glands, AAH, and cancer (mean number of stained glands, 43%). Total acidic mucin was more common in AAH (63% of cases; mean, 11% of glands) and adenocarcinoma (60% of cases; mean, 30% of glands) than in benign glands (0% of cases). Similarly, nonsulfated acidic mucin was more common in AAH (63% of cases; mean, 12% glands) and adenocarcinoma (60% of cases; mean, 8% of glands) than in benign glands (0% of cases); the pattern and intensity of staining for nonsulfated acidic mucin appeared to be similar to that for total acidic mucin in AAH and cancer. These findings indicate that there is a close relationship in mucin expression between AAH and well-differentiated adenocarcinoma. Identification of acidic mucin should be used cautiously as an adjunct in the diagnosis of adenocarcinoma but is useful in separating some cases of AAH and adenocarcinoma from benign prostatic epithelium.
Kenji Suzuki - One of the best experts on this subject based on the ideXlab platform.
-
association of cyp19a1 polymorphisms with risks for Atypical Adenomatous Hyperplasia and bronchioloalveolar carcinoma in the lungs
Carcinogenesis, 2010Co-Authors: Takashi Kohno, Kenji Suzuki, Ryutaro Kakinuma, Motoki Iwasaki, Taiki Yamaji, Hideo Kunitoh, Yoko Shimada, Kouya Shiraishi, Yoshio Kasuga, Gerson Shigeaki HamadaAbstract:Abstract Estrogen has been indicated to play an etiological role in the development of lung adenocarcinoma (ADC), particularly bronchioloalveolar carcinoma (BAC), a type of ADC that develops from a benign Adenomatous lesion, Atypical Adenomatous Hyperplasia (AAH). Polymorphisms in the CYP19A1 gene cause interindividual differences in estrogen levels. Here, 13 CYP19A1 single-nucleotide polymorphisms (SNPs) were examined for associations with lung AAH risk. AAH is detected as ground-glass opacity (GGO) by computed tomography (CT) examination, and this study consisted of 100 individuals diagnosed with GGO in their lungs among 3088 CT-based cancer screening examinees and 424 without. Minor allele carriers for the rs3764221 SNP showed an elevated risk for GGO [odds ratio (OR) = 1.72, P = 0.017]. Associations of this SNP with risks for lung AAH and BAC in the lungs were next examined using 359 ADC cases whose resected lung lobes were subjected to a histological examination for AAH accompaniment and the presence of BAC components and 330 controls without cancer. The ORs were also increased for lung ADC accompanied by AAH (OR = 1.74, P = 0.029) as well as lung ADC with BAC components (OR = 1.41, P = 0.091). The minor allele was associated with an increased circulating estradiol level (P = 0.079) in a population of 363 postmenopausal women without cancer. These results indicate that CYP19A1 polymorphisms are involved in the risk for lung AAH and BAC in the lungs by causing differences in estrogen levels.
-
loss of heterozygosity on chromosomes 9q and 16p in Atypical Adenomatous Hyperplasia concomitant with adenocarcinoma of the lung
American Journal of Pathology, 2001Co-Authors: Kazuya Takamochi, Tomoyuki Yokose, Kenji Suzuki, Yutaka Nishiwaki, Kanji Nagai, A Ochiai, Tsutomu Ogura, Hidenori Kawasaki, Yukiko Kurashima, Hiroyasu EsumiAbstract:Atypical Adenomatous Hyperplasia (AAH) has recently been implicated as a precursor to lung adenocarcinoma. We previously reported loss of heterozygosity (LOH) in tuberous sclerosis (TSC) gene-associated regions to frequently be observed in lung adenocarcinoma with multiple AAHs. In this study, we analyzed LOH in four microsatellite loci on 9q, including the TSC1 gene-associated region, and four loci on 16p, including the TSC2 gene-associated region, in both 18 AAHs and 17 concomitant lung adenocarcinomas from 11 patients. Seven of 18 (39%) AAHs and 9 of 17 (53%) adenocarcinomas displayed LOH on 9q. Five (28%) AAHs and seven (41%) adenocarcinomas harbored LOH at loci adjacent to the TSC1 gene. Four of 18 (22%) AAHs and 6 of 17 (35%) adenocarcinomas displayed LOH on 16p. One (6%) AAH and five (29%) adenocarcinomas harbored LOH at loci adjacent to the TSC2 gene. These findings may indicate a causal relationship of LOH on 9q and 16p in a fraction of AAH lesions and adenocarcinomas of the lung. Especially, the frequencies of LOH on 9q and at the TSC1 gene-associated region were high. The TSC1 gene or another neighboring tumor suppressor gene on 9q might be involved in an early stage of the pathogenesis of lung adenocarcinoma.
-
monoclonality of Atypical Adenomatous Hyperplasia of the lung
American Journal of Pathology, 1999Co-Authors: Seiji Niho, Tomoyuki Yokose, Kenji Suzuki, Tetsuro Kodama, Yutaka Nishiwaki, Kiyoshi MukaiAbstract:Atypical Adenomatous Hyperplasia (AAH) of the lung has been postulated as a possible precursor lesion of bronchioloalveolar carcinoma (BAC). The clonality of AAHs from seven female patients was analyzed to determine whether AAH is a monoclonal expansion. All AAHs were identified in lungs surgically resected for BAC. The clonality of the BAC and bronchiolar metaplasia in each case was also analyzed. Approximately 500 cells in each lesion were precisely microdissected from methanol-fixed sections. Adjacent normal lung tissue was collected as a normal control. DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor gene (HUMARA). HUMARA was found to be amplified with or without previous digestion by the methylation-sensitive restriction endonuclease HpaII. Five cases were informative. All 10 AAHs and 7 BACs obtained from the informative cases showed monoclonality, whereas the control cells showed polyclonality. Three different AAH lesions in a single case showed both possible patterns of monoclonality. BAC and contiguous AAH showed identical monoclonality in two cases. Two lesions of bronchiolar metaplasia, which was considered reactive, were polyclonal. Our results demonstrated the monoclonal nature of AAH, and this finding suggests that AAH is a precursor of BAC or a preneoplastic condition.
-
Case report Synchronous double primary lung carcinomas associated with multiple Atypical Adenomatous Hyperplasia
1998Co-Authors: Kenji Suzuki, Tomoyuki Yokose, Yutaka Nishiwaki, Kenro Takahashi, Junji Yoshida, Mitsuyo Nishimura, Kanji NagaiAbstract:A 71-year-old woman with synchronous bilateral primary lung carcinomas accompanied by multiple Atypical Adenomatous Hyperplasias is described. The patient was found to have bilateral tumors during preoperative workup for the previously detected well differentiated adenocarcinoma of the right lung. Thoracoscopic wedge resection of the left upper lobe was performed to obtain a definitive diagnosis of the left lesion. Although intraoperative diagnosis was made by frozen section as Atypical papillary lesion, postoperative diagnosis of this lesion was changed to well differentiated adenocarcinoma accompanied by surrounding Atypical Adenomatous Hyperplasia (AAH). We diagnosed that the bilateral lesions were synchronous primary well differentiated adenocarcinomas independent to each other based on the criteria of Martini and Melamed and performed right upper and mediastinal lymph node dissection. The resected lobe contained not only the primary adenocarcinoma but also multiple small gray nodules which were diagnosed as AAHs. In summary, it was diagnosed that the patient had synchronous double primary lung adenocarcinomas of T1 N0 M0 pathological stage and 12 solitary Atypical Adenomatous Hyperplasias. The patient is doing well with no signs of recurrence 24 months after the operation. This case might be an example of the adenoma-carcinoma sequence of lung cancer. A careful follow-up study is mandatory for this patient with special regard to the further development of lung carcinoma in the future. © 1998 Elsevier Science Ireland Ltd. All rights reserved.
-
loss of heterozygosity in the tuberous sclerosis gene associated regions in adenocarcinoma of the lung accompanied by multiple Atypical Adenomatous Hyperplasia
International Journal of Cancer, 1998Co-Authors: Kenji Suzuki, Tomoyuki Yokose, Tetsuro Kodama, Yutaka Nishiwaki, Kiyoshi Mukai, Kanji Nagai, Tsutomu Ogura, Hiroyasu EsumiAbstract:To investigate the potential allelic loss of tumor suppressor gene loci in the tuberous sclerosis complex (TSC)-associated regions located on the long arm of chromosome 9 (9q) and on the short arm of chromosome 16 (16p) in human lung carcinoma, we analyzed 21 paired normal and tumor DNAs with 11 polymorphic markers on the chromosomes. All tumors were adenocarcinoma of the lung, which included 9 adenocarcinomas with associated multiple Atypical Adenomatous Hyperplasia (AAH). A precise microdissection technique followed by polymerase chain reaction (PCR) amplification to prevent under-evaluation of loss of heterozygosity (LOH) was used. Twelve of the 21 (57%) adenocarcinomas displayed LOH on 9q. Five of the 21 adenocarcinomas (24%) showed LOH at all informative loci on 9q, whereas 7 (33%) demonstrated partial LOH on 9q34. Among these 21, 5 (24%) showed partial LOH between D9S149 and D9S150, where TSC1 is located. The incidence of associated AAH was significantly higher in adenocarcinoma harboring a partial LOH in the TSC1-associated region (p = 0.0048). Twelve of the 21 (57%) adenocarcinomas displayed LOH on 16p. No significant differences in the clinico-pathological characteristics could be discerned between adenocarcinomas with and without LOH on 16p. When combining these data, a partial LOH at TSC1- and/or TSC2-associated loci was observed more frequently in cases with well-differentiated adenocarcinoma (p = 0.086) and associated AAH (p = 0.081). In conclusion, our results suggest that the TSC-associated regions are new candidate loci for tumor suppressor genes in lung adenocarcinoma, especially when it is accompanied by multiple AAH. Int. J. Cancer (Pred. Oncol.) 79:384–389, 1998. © 1998 Wiley-Liss, Inc.
Tomoyuki Yokose - One of the best experts on this subject based on the ideXlab platform.
-
Atypical Adenomatous Hyperplasia of the lung in autopsy cases.
Lung cancer (Amsterdam Netherlands), 2020Co-Authors: Tomoyuki Yokose, Kozo Tanno, Kentaro Yamazaki, A OchiaiAbstract:Atypical Adenomatous Hyperplasia (AAH) is a possible precursor lesion of adenocarcinoma of the lung, but very few reports of AAH have focused on the autopsy lung. We intended to clarify the characteristics of AAH in the general population by using 207 autopsy cases, ranging in age from 0 to 90 years old. A total of 179 eligible cases (86.5%) and 1265 tissue slides (7.0 per case) was examined independently by two pathologists. One hundred seventy-nine autopsy cases consisted of 125 males and 54 females, whose median ages were 38 (range 0-90) and 31 (range 0-81) years old, respectively. AAH was microscopically found in five of 179 autopsy cases (2.8%). The male/female ratio was 5/0 and age distribution was 52-63 years of age (median 57). One of five cases with AAH harbored esophageal carcinoma, but the others had no present or previous malignant neoplasm. One of five lesions was high grade and the others were low grade. All five cases showed positive immunoreactivity for proSP-C, a type II pneumocytes marker, but not for p53, Ki-67 or CEA. The incidence of AAH was very low in the general autopsy cases, as compared with the previously reported surgically resected lung and senile autopsy cases, and AAH seems to occur after middle age in general.
-
loss of heterozygosity on chromosomes 9q and 16p in Atypical Adenomatous Hyperplasia concomitant with adenocarcinoma of the lung
American Journal of Pathology, 2001Co-Authors: Kazuya Takamochi, Tomoyuki Yokose, Kenji Suzuki, Yutaka Nishiwaki, Kanji Nagai, A Ochiai, Tsutomu Ogura, Hidenori Kawasaki, Yukiko Kurashima, Hiroyasu EsumiAbstract:Atypical Adenomatous Hyperplasia (AAH) has recently been implicated as a precursor to lung adenocarcinoma. We previously reported loss of heterozygosity (LOH) in tuberous sclerosis (TSC) gene-associated regions to frequently be observed in lung adenocarcinoma with multiple AAHs. In this study, we analyzed LOH in four microsatellite loci on 9q, including the TSC1 gene-associated region, and four loci on 16p, including the TSC2 gene-associated region, in both 18 AAHs and 17 concomitant lung adenocarcinomas from 11 patients. Seven of 18 (39%) AAHs and 9 of 17 (53%) adenocarcinomas displayed LOH on 9q. Five (28%) AAHs and seven (41%) adenocarcinomas harbored LOH at loci adjacent to the TSC1 gene. Four of 18 (22%) AAHs and 6 of 17 (35%) adenocarcinomas displayed LOH on 16p. One (6%) AAH and five (29%) adenocarcinomas harbored LOH at loci adjacent to the TSC2 gene. These findings may indicate a causal relationship of LOH on 9q and 16p in a fraction of AAH lesions and adenocarcinomas of the lung. Especially, the frequencies of LOH on 9q and at the TSC1 gene-associated region were high. The TSC1 gene or another neighboring tumor suppressor gene on 9q might be involved in an early stage of the pathogenesis of lung adenocarcinoma.
-
Atypical Adenomatous Hyperplasia of the lung in autopsy cases
Lung Cancer, 2001Co-Authors: Tomoyuki Yokose, Kozo Tanno, Kentaro Yamazaki, A OchiaiAbstract:Abstract Background: Atypical Adenomatous Hyperplasia (AAH) is a possible precursor lesion of adenocarcinoma of the lung, but very few reports of AAH have focused on the autopsy lung. Methods: We intended to clarify the characteristics of AAH in the general population by using 207 autopsy cases, ranging in age from 0 to 90 years old. Results: A total of 179 eligible cases (86.5%) and 1265 tissue slides (7.0 per case) was examined independently by two pathologists. One hundred seventy-nine autopsy cases consisted of 125 males and 54 females, whose median ages were 38 (range 0–90) and 31 (range 0–81) years old, respectively. AAH was microscopically found in five of 179 autopsy cases (2.8%). The male/female ratio was 5/0 and age distribution was 52–63 years of age (median 57). One of five cases with AAH harbored esophageal carcinoma, but the others had no present or previous malignant neoplasm. One of five lesions was high grade and the others were low grade. All five cases showed positive immunoreactivity for proSP-C, a type II pneumocytes marker, but not for p53, Ki-67 or CEA. Conclusions: The incidence of AAH was very low in the general autopsy cases, as compared with the previously reported surgically resected lung and senile autopsy cases, and AAH seems to occur after middle age in general.
-
Atypical Adenomatous Hyperplasia of the lung a clinicopathological study of 118 cases including cases with multiple Atypical Adenomatous Hyperplasia
Thorax, 2001Co-Authors: R Nakahara, Tomoyuki Yokose, Yutaka Nishiwaki, Kanji Nagai, A OchiaiAbstract:BACKGROUND Atypical Adenomatous Hyperplasia (AAH) of the lung is a putative precursor lesion of adenocarcinoma, according to many immunohistochemical and genetical studies, but few clinicopathological studies on a large number of cases have been reported. The aim of this study was to clarify the clinicopathological characteristics of lung cancer patients with AAH lesions. METHODS A retrospective study was carried out on 508 consecutive primary lung cancer patients operated on at National Cancer Center Hospital East. The relationship between the number and location of AAH lesions and the clinicopathological features of the lung cancer patients was analysed statistically. RESULTS A total of 311 AAH lesions were found in 118 (23.2%) of the 508 cases. AAH lesions were detected in 121 of 572 lobes examined, usually in both upper lobes, and occurred most frequently in patients with adenocarcinoma (OR 2.97; 95% CI 1.82 to 4.85). AAH lesions were more frequently detected in patients with multiple primary carcinomas than in those with a single carcinoma (OR 3.06; 95% CI 1.56 to 6.00). The presence of AAH lesions was not significantly correlated with sex, age, smoking status, familial history of malignancy, or preceding malignancy. Patients with multiple AAH lesions were found to have a significantly higher frequency of preceding malignancies. CONCLUSIONS The present study highlights the clinicopathological characteristics of AAH lesions, showing them to be significantly associated with both adenocarcinoma and multiple primary carcinoma of the lung and suggesting common factors in the histogenesis of multiple AAH lesions and preceding malignancy.
-
high prevalence of Atypical Adenomatous Hyperplasia of the lung in autopsy specimens from elderly patients with malignant neoplasms
Lung Cancer, 2000Co-Authors: Tomoyuki Yokose, A OchiaiAbstract:Atypical Adenomatous Hyperplasia (AAH) is a possible precursor lesion of adenocarcinoma of the lung, but there have been no reports of AAH focusing on autopsy studies of the lungs of elderly patients, who have higher lung cancer mortality rates. We intended to clarify the characteristics of AAH in the general elderly population on the basis of the findings in autopsy cases. A total of 19 AAH lesions were found microscopically in 16 out of 241 autopsy cases (6.6%). AAH was found in only two cases of adenocarcinoma among 28 lung cancer cases. p53 immunoreactivity was observed in one of 11 low-grade AAH lesions (9.1%), but in three of four high-grade AAH lesions (75%, P=0.03) and the cases of high-grade AAH were more frequently positive for Ki-67 and CEA than the low-grade cases and less positive for pro-surfactant apoprotein C. Four of 123 patients without malignant neoplasms (3.4%) and 12 of 118 patients with malignant neoplasms (11.1%) had AAH (P=0.03). The finding that AAH was more common in the cases with malignancy than in those without malignancy indicated that genesis of AAH may be closely associated with that of malignant neoplasms.
Rodolfo Montironi - One of the best experts on this subject based on the ideXlab platform.
-
molecular evidence supporting the precursor nature of Atypical Adenomatous Hyperplasia of the prostate
Molecular Carcinogenesis, 2019Co-Authors: Liang Cheng, Antonio Lopezbeltran, Darrell D Davidson, Rodolfo Montironi, Mingsheng Wang, Shaobo ZhangAbstract:: Atypical Adenomatous Hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low-grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. In this study, we investigate telomere shortening in AAH (n = 93), high-grade prostatic intraepithelial neoplasia (HGPIN) ( n = 68), and prostatic adenocarcinoma (PCA) ( n = 70) using quantitative fluorescence in situ hybridization. Twenty percent (19 of 93) of AAH specimens, 68% (46 of 68) of HGPIN, and 83% (58 of 70) of PCA showed significant telomere shortening. Thirty-two percent of AAH lesions had α-methylacyl-CoA racemase (AMACR) expression, a sensitive and specific marker for HGPIN and PCA. AMACR expression in AAH was seen more frequently in AAH foci with telomere shortening or coexisting PCA. Our findings indicate that a subset of AAH lesions have telomere shortening and AMACR expression, suggesting that these foci may be precursors for PCA.
-
Atypical Adenomatous Hyperplasia of prostate lacks tmprss2 erg gene fusion
The American Journal of Surgical Pathology, 2013Co-Authors: Liang Cheng, Antonio Lopezbeltran, Darrell D Davidson, Gregory T Maclennan, Rodolfo Montironi, Mingsheng Wang, Lee Ann Baldridge, Shaobo ZhangAbstract:: Atypical Adenomatous Hyperplasia (AAH) is a distinct entity in prostate pathology, defined as a well-circumscribed lobule of closely packed crowded small glands or acini. Although it has been proposed as a precursor lesion to prostate cancer, the biological nature of AAH is currently uncertain. The TMPRSS2-ERG fusion gene is a common recurrent chromosomal rearrangement in prostate cancer and in its precursor lesion, prostatic intraepithelial neoplasia. The prevalence of TMPRSS2-ERG alteration in AAH is unknown. Fifty-five separate prostate specimens containing AAH were investigated by fluorescence in situ hybridization and immunohistochemistry for TMPRSS2-ERG rearrangement. TMPRSS2-ERG rearrangements were not identified in AAH either by fluorescence in situ hybridization or by immunohistochemistry.
-
is Atypical Adenomatous Hyperplasia of the prostate a precursor lesion
The Prostate, 2011Co-Authors: Chen Zhang, Antonio Lopezbeltran, Gregory T Maclennan, Rodolfo Montironi, Mingsheng Wang, Shaobo Zhang, Yan Li, Kenneth A Iczkowski, Liang ChengAbstract:BACKGROUND Alpha-methylacyl-CoA racemase (AMACR) is highly expressed in prostatic adenocarcinoma. The precursor nature of Atypical Adenomatous Hyperplasia (AAH) is uncertain. METHODS One hundred twenty-one AAH foci from 101 patients who underwent transurethral prostatic resection or prostatectomy were immunohistochemically analyzed for AMACR, high molecular weight cytokeratin 34βE12, and p63 expression by a triple antibody (PIN4) cocktail stain. RESULTS Sixty-eight foci (56%) of AAH showed no AMACR immunostaining. Fourteen cases (12%) showed weak AMACR immunoreactivity in 1–9% of lesional cells. Sixteen cases (13%) showed strong immunopositivity for AMACR in >50% of lesional cells. AMACR expression in AAH was significantly higher in cases in which coexisting PCA was present, compared with its expression in AAH foci without coexisting PCA (P = 0.03). Strong diffuse AMACR positivity in over 50% of lesional cells was seen almost exclusively in AAH foci with coexisting PCA (P = 0.002). AMACR expression in AAH showed no correlation with patient age (P = 0.38), specimen type (P = 0.35), prostate weight (P = 0.80), zonal location (P = 0.50), distance to cancer (P = 0.28), Gleason score (P = 0.06), or pathologic stage (P = 0.23). Increased AMACR expression showed a negative correlation with the size of AAH foci (P = 0.03). All AAH lesions showed fragmented basal cell layers, highlighted by p63 and high molecular weight cytokeratin staining. CONCLUSIONS A significant percentage of AAH cases show stronger and more extensive AMACR expression when associated with prostatic adenocarcinoma, as compared to AAH foci found without coexisting prostate cancer. Our data provide additional evidence linking AAH to prostatic adenocarcinoma. Prostate 71:1746–1751, 2011. © 2011 Wiley Periodicals, Inc.
-
Atypical Adenomatous Hyperplasia adenosis of the prostate dna ploidy analysis and immunophenotype
International Journal of Surgical Pathology, 2005Co-Authors: Antonio Lopezbeltran, Junqi Qian, Rodolfo Montironi, Rafael J Luque, David G BostwickAbstract:Atypical Adenomatous Hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular Hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34β-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feul gen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular Hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular Hyperplasia and AAH (p<0.001) and carci...
-
the significance of Atypical Adenomatous Hyperplasia and prostatic intraepithelial neoplasia for the development of prostate carcinoma an update
Virchows Archiv, 1995Co-Authors: B Helpap, David G Bostwick, Rodolfo MontironiAbstract:The term prostatic intraepithelial neoplasia (PIN) is an accepted diagnosis in pathology of the prostate. The diagnostic difference between Atypical Adenomatous Hyperplasia (AAH) and adenosis is still under debate. A number of questions remain about the significance of grading of AAH and PIN, the biology of AAH and PIN as precursors of carcinoma, the possibility of treatment of AAH and PIN and whether AAH- and PIN-associated cancers differ from non-associated carcinoma. This paper reviews the results and discussions at the First International Consultation Meeting on Atypical Adenomatous Hyperplasia and Prostatic Intraepithelial Neoplasia and the Origins of the Prostatic Carcinomas. AAH is an architectural atypia of the prostate. The histological and cytological features of AAH are intermediate between BPH and low-grade carcinoma of the prostate. Cell kinetic findings show no distinct neoplastic pattern. AAH may be a precursor of transition zone carcinoma but the findings to date are inconclusive. Follow up studies should address whether the association of AAH and carcinoma is incidental or whether transition occurs between AAH and carcinoma. In contrast, PIN is an accepted preneoplastic lesion and the most likely precursor of the dorso-peripheral zone carcinoma. The diagnosis of high-grade PIN is clinically important, because high-grade PIN is associated with carcinoma in a high percentage of patients (38–100%). AAH- and PIN-associated cancers may not differ from other prostatic cancers. At present treatment for AAH and PIN without carcinoma is not indicated, but high-grade PIN warrants surveillance and follow up of the patient to identify a possible coexisting cancer. It must be stressed that AAH and PIN are multifocal lesions and both are age-associated.
Kanji Nagai - One of the best experts on this subject based on the ideXlab platform.
-
loss of heterozygosity on chromosomes 9q and 16p in Atypical Adenomatous Hyperplasia concomitant with adenocarcinoma of the lung
American Journal of Pathology, 2001Co-Authors: Kazuya Takamochi, Tomoyuki Yokose, Kenji Suzuki, Yutaka Nishiwaki, Kanji Nagai, A Ochiai, Tsutomu Ogura, Hidenori Kawasaki, Yukiko Kurashima, Hiroyasu EsumiAbstract:Atypical Adenomatous Hyperplasia (AAH) has recently been implicated as a precursor to lung adenocarcinoma. We previously reported loss of heterozygosity (LOH) in tuberous sclerosis (TSC) gene-associated regions to frequently be observed in lung adenocarcinoma with multiple AAHs. In this study, we analyzed LOH in four microsatellite loci on 9q, including the TSC1 gene-associated region, and four loci on 16p, including the TSC2 gene-associated region, in both 18 AAHs and 17 concomitant lung adenocarcinomas from 11 patients. Seven of 18 (39%) AAHs and 9 of 17 (53%) adenocarcinomas displayed LOH on 9q. Five (28%) AAHs and seven (41%) adenocarcinomas harbored LOH at loci adjacent to the TSC1 gene. Four of 18 (22%) AAHs and 6 of 17 (35%) adenocarcinomas displayed LOH on 16p. One (6%) AAH and five (29%) adenocarcinomas harbored LOH at loci adjacent to the TSC2 gene. These findings may indicate a causal relationship of LOH on 9q and 16p in a fraction of AAH lesions and adenocarcinomas of the lung. Especially, the frequencies of LOH on 9q and at the TSC1 gene-associated region were high. The TSC1 gene or another neighboring tumor suppressor gene on 9q might be involved in an early stage of the pathogenesis of lung adenocarcinoma.
-
Atypical Adenomatous Hyperplasia of the lung a clinicopathological study of 118 cases including cases with multiple Atypical Adenomatous Hyperplasia
Thorax, 2001Co-Authors: R Nakahara, Tomoyuki Yokose, Yutaka Nishiwaki, Kanji Nagai, A OchiaiAbstract:BACKGROUND Atypical Adenomatous Hyperplasia (AAH) of the lung is a putative precursor lesion of adenocarcinoma, according to many immunohistochemical and genetical studies, but few clinicopathological studies on a large number of cases have been reported. The aim of this study was to clarify the clinicopathological characteristics of lung cancer patients with AAH lesions. METHODS A retrospective study was carried out on 508 consecutive primary lung cancer patients operated on at National Cancer Center Hospital East. The relationship between the number and location of AAH lesions and the clinicopathological features of the lung cancer patients was analysed statistically. RESULTS A total of 311 AAH lesions were found in 118 (23.2%) of the 508 cases. AAH lesions were detected in 121 of 572 lobes examined, usually in both upper lobes, and occurred most frequently in patients with adenocarcinoma (OR 2.97; 95% CI 1.82 to 4.85). AAH lesions were more frequently detected in patients with multiple primary carcinomas than in those with a single carcinoma (OR 3.06; 95% CI 1.56 to 6.00). The presence of AAH lesions was not significantly correlated with sex, age, smoking status, familial history of malignancy, or preceding malignancy. Patients with multiple AAH lesions were found to have a significantly higher frequency of preceding malignancies. CONCLUSIONS The present study highlights the clinicopathological characteristics of AAH lesions, showing them to be significantly associated with both adenocarcinoma and multiple primary carcinoma of the lung and suggesting common factors in the histogenesis of multiple AAH lesions and preceding malignancy.
-
Case report Synchronous double primary lung carcinomas associated with multiple Atypical Adenomatous Hyperplasia
1998Co-Authors: Kenji Suzuki, Tomoyuki Yokose, Yutaka Nishiwaki, Kenro Takahashi, Junji Yoshida, Mitsuyo Nishimura, Kanji NagaiAbstract:A 71-year-old woman with synchronous bilateral primary lung carcinomas accompanied by multiple Atypical Adenomatous Hyperplasias is described. The patient was found to have bilateral tumors during preoperative workup for the previously detected well differentiated adenocarcinoma of the right lung. Thoracoscopic wedge resection of the left upper lobe was performed to obtain a definitive diagnosis of the left lesion. Although intraoperative diagnosis was made by frozen section as Atypical papillary lesion, postoperative diagnosis of this lesion was changed to well differentiated adenocarcinoma accompanied by surrounding Atypical Adenomatous Hyperplasia (AAH). We diagnosed that the bilateral lesions were synchronous primary well differentiated adenocarcinomas independent to each other based on the criteria of Martini and Melamed and performed right upper and mediastinal lymph node dissection. The resected lobe contained not only the primary adenocarcinoma but also multiple small gray nodules which were diagnosed as AAHs. In summary, it was diagnosed that the patient had synchronous double primary lung adenocarcinomas of T1 N0 M0 pathological stage and 12 solitary Atypical Adenomatous Hyperplasias. The patient is doing well with no signs of recurrence 24 months after the operation. This case might be an example of the adenoma-carcinoma sequence of lung cancer. A careful follow-up study is mandatory for this patient with special regard to the further development of lung carcinoma in the future. © 1998 Elsevier Science Ireland Ltd. All rights reserved.
-
loss of heterozygosity in the tuberous sclerosis gene associated regions in adenocarcinoma of the lung accompanied by multiple Atypical Adenomatous Hyperplasia
International Journal of Cancer, 1998Co-Authors: Kenji Suzuki, Tomoyuki Yokose, Tetsuro Kodama, Yutaka Nishiwaki, Kiyoshi Mukai, Kanji Nagai, Tsutomu Ogura, Hiroyasu EsumiAbstract:To investigate the potential allelic loss of tumor suppressor gene loci in the tuberous sclerosis complex (TSC)-associated regions located on the long arm of chromosome 9 (9q) and on the short arm of chromosome 16 (16p) in human lung carcinoma, we analyzed 21 paired normal and tumor DNAs with 11 polymorphic markers on the chromosomes. All tumors were adenocarcinoma of the lung, which included 9 adenocarcinomas with associated multiple Atypical Adenomatous Hyperplasia (AAH). A precise microdissection technique followed by polymerase chain reaction (PCR) amplification to prevent under-evaluation of loss of heterozygosity (LOH) was used. Twelve of the 21 (57%) adenocarcinomas displayed LOH on 9q. Five of the 21 adenocarcinomas (24%) showed LOH at all informative loci on 9q, whereas 7 (33%) demonstrated partial LOH on 9q34. Among these 21, 5 (24%) showed partial LOH between D9S149 and D9S150, where TSC1 is located. The incidence of associated AAH was significantly higher in adenocarcinoma harboring a partial LOH in the TSC1-associated region (p = 0.0048). Twelve of the 21 (57%) adenocarcinomas displayed LOH on 16p. No significant differences in the clinico-pathological characteristics could be discerned between adenocarcinomas with and without LOH on 16p. When combining these data, a partial LOH at TSC1- and/or TSC2-associated loci was observed more frequently in cases with well-differentiated adenocarcinoma (p = 0.086) and associated AAH (p = 0.081). In conclusion, our results suggest that the TSC-associated regions are new candidate loci for tumor suppressor genes in lung adenocarcinoma, especially when it is accompanied by multiple AAH. Int. J. Cancer (Pred. Oncol.) 79:384–389, 1998. © 1998 Wiley-Liss, Inc.
-
synchronous double primary lung carcinomas associated with multiple Atypical Adenomatous Hyperplasia
Lung Cancer, 1998Co-Authors: Kenji Suzuki, Tomoyuki Yokose, Yutaka Nishiwaki, Kenro Takahashi, Junji Yoshida, Mitsuyo Nishimura, Kanji NagaiAbstract:Abstract A 71-year-old woman with synchronous bilateral primary lung carcinomas accompanied by multiple Atypical Adenomatous Hyperplasias is described. The patient was found to have bilateral tumors during preoperative workup for the previously detected well differentiated adenocarcinoma of the right lung. Thoracoscopic wedge resection of the left upper lobe was performed to obtain a definitive diagnosis of the left lesion. Although intraoperative diagnosis was made by frozen section as Atypical papillary lesion, postoperative diagnosis of this lesion was changed to well differentiated adenocarcinoma accompanied by surrounding Atypical Adenomatous Hyperplasia (AAH). We diagnosed that the bilateral lesions were synchronous primary well differentiated adenocarcinomas independent to each other based on the criteria of Martini and Melamed and performed right upper and mediastinal lymph node dissection. The resected lobe contained not only the primary adenocarcinoma but also multiple small gray nodules which were diagnosed as AAHs. In summary, it was diagnosed that the patient had synchronous double primary lung adenocarcinomas of T1 N0 M0 pathological stage and 12 solitary Atypical Adenomatous Hyperplasias. The patient is doing well with no signs of recurrence 24 months after the operation. This case might be an example of the adenoma-carcinoma sequence of lung cancer. A careful follow-up study is mandatory for this patient with special regard to the further development of lung carcinoma in the future.
