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Nicholas Coleman - One of the best experts on this subject based on the ideXlab platform.
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Minichromosome Maintenance Protein 2 positive portal tract lymphocytes distinguish acute cellular rejection from hepatitis c virus recurrence after liver transplantation
Liver Transplantation, 2009Co-Authors: Esther Unitt, Nicholas Coleman, Susan E Davies, William Gelson, Graeme J M AlexanderAbstract:Hepatitis C virus (HCV) is a leading indication for liver transplantation worldwide, but graft infection with HCV frequently leads to hepatic fibrosis. Acute cellular rejection (ACR) can be difficult to distinguish confidently from HCV, even with histology, but accurate diagnosis is critical because treatment of ACR may accelerate HCV-related graft injury. Immunohistochemistry was undertaken on 99 liver biopsies from 31 patients with HCV graft infection, 22 patients with ACR, and 11 patients with HCV infection and unexplained graft dysfunction to investigate whether lymphocyte expression of Minichromosome Maintenance Protein-2 (Mcm-2), a marker of licensed cell cycle entry, assessed in a novel semiautomated system could distinguish between ACR and graft infection with HCV. The portal tract area was greater in ACR than in HCV graft infection (P = 0.027), but there was considerable overlap. However, both the number of Mcm-2-positive lymphocytes per portal tract and the number of Mcm-2-positive lymphocytes per millimeter squared of portal tract distinguished between ACR and HCV graft infection (P < 0.0001). A cutoff value of 107 positive cells per portal tract had a sensitivity of 81.8% and a specificity of 91.9% (positive predictive value of 66.67% and negative predictive value of 95.75%). Of 11 HCV-infected patients with an uncertain diagnosis, 7 were deemed ultimately to have HCV graft infection, and 4 had superimposed corticosteroid-responsive ACR. The number of Mcm-2-positive cells per portal tract and per millimeter squared of portal tract again distinguished clearly between the groups (P = 0.012). In conclusion, lymphocyte Mcm-2 expression is a useful adjunct to histology in differentiating between HCV graft infection and ACR. Patients with a low number of Mcm-2-positive portal tract lymphocytes are less likely to have ACR.
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hepatocyte expression of Minichromosome Maintenance Protein 2 predicts fibrosis progression after transplantation for chronic hepatitis c virus a pilot study
Liver Transplantation, 2005Co-Authors: Aileen Marshall, Lesley S Morris, Sarah L Vowler, Nicholas Coleman, Simon M Rushbrook, Ian Scott, Susan E Davies, Graeme J M AlexanderAbstract:Although graft infection with hepatitis C virus (HCV) occurs in virtually all patients transplanted for HCV-related liver disease, the outcome ranges from minimal disease to the rapid development of cirrhosis. Induction of hepatocyte cell cycle entry followed by inhibition of cell cycle progression has been proposed as a potential mechanism whereby HCV may cause hepatocyte dysfunction and may promote fibrogenesis. The aim of this study was to assess whether early hepatocyte cell cycle entry might predict subsequent fibrosis progression in patients with graft HCV infection after liver transplantation. Liver biopsies from 21 liver transplant recipients diagnostic of graft HCV infection but before development of significant fibrosis were studied. Patients were classed as nonprogressors, intermediate progressors, or rapid progressors according to the rate of fibrosis progression calculated from the most recent biopsy. Minichromosome Maintenance Protein 2 (Mcm-2), a highly sensitive and specific marker of cell cycle entry, and cyclin-dependent kinase inhibitor p21 were detected by immunohistochemistry. Hepatocyte Mcm-2 expression increased significantly according to rate of fibrosis. For nonprogressors, the median percentage of positive hepatocytes was 5.3% (range, 0.92%-11.2%) compared with 20.7% (4.6%-43.7%) in intermediate progressors and 23.7% (11.6%-55.2%) in rapid progressors (P = 0.002). By contrast, there was no evidence of a difference in hepatocyte p21 expression. Median values and ranges were 3.4% (range, 1.1%-30%), 13.3% (range, 1.4%-42.3%), and 11.8% (range, 7.6%-52.3%) for nonprogressors, intermediate progressors, and rapid progressors, respectively (P = 0.11). In conclusion, hepatocyte cell cycle entry may be important in the pathogenesis of posttransplant HCV hepatitis. Early assessment of hepatocyte Mcm-2 expression could help identify patients at high risk for progressive fibrosis before it occurs.
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increased expression of Minichromosome Maintenance Protein 2 in active inflammatory bowel disease
Colorectal Disease, 2004Co-Authors: R J Davies, Lesley S Morris, Sarah L Vowler, K Bird, I S Scott, S M Rushbrook, M Arends, R Miller, Nicholas ColemanAbstract:Objective Minichromosome Maintenance Protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity. Materials and methods For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal). Results The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032). Conclusions There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.
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Minichromosome Maintenance Protein in myxofibrosarcoma
Modern Pathology, 2004Co-Authors: James D Sington, Alex Freeman, Lesley S Morris, Sarah L Vowler, Barbara N Arch, Cyril Fisher, Nicholas ColemanAbstract:Histopathological assessment of myxofibrosarcoma may be difficult, especially on the basis of a small core biopsy, which enables only a crude evaluation of grade and prognosis. We have tested the hypothesis that determination of cell cycle state may assist in the diagnostic assessment of myxofibrosarcoma. We have studied 51 cases of high-grade (n=20), intermediate-grade (n=21), and low-grade (n=10) myxofibrosarcomas, as well as nine cases of benign myxoma. Cell cycle state within tumors was determined by immunostaining for the recently described marker Minichromosome Maintenance Protein 2 (MCM2), together with Ki67. Labelling indices for both markers were correlated with tumor grade, mitotic index, and time to first recurrence. The MCM2 labelling indices were significantly higher than the Ki-67 labelling indices. Both indices showed a significant correlation with the mitotic index and both showed significant increases with increasing grade of myxofibrosarcoma. The MCM2 labelling index (but not the Ki67 labelling index) showed a significant inverse exponential correlation with the time to first recurrence. Myxoid and cellular areas showed no difference in the MCM2 and Ki-67 labeling index, suggesting that clinically useful information could be obtained from any component of a myxofibrosarcoma sampled in a needle biopsy and/or cytological specimen. We therefore suggest that assessment of cell cycle state may be a useful diagnostic adjunct in the histopathological assessment of myxofibrosarcoma, by enabling more accurate determination of grade and prediction of outcome.
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Minichromosome Maintenance Protein 2 is a strong independent prognostic marker in breast cancer
Journal of Clinical Oncology, 2003Co-Authors: Michael A Gonzalez, Lesley S Morris, Sarah L Vowler, K Bird, S E Pinder, Grace Callagy, J A Bell, Ronald A Laskey, Nicholas ColemanAbstract:Purpose: To test the hypothesis that prognostic information in breast cancer may be derived from an accurate assessment of epithelial cell cycle entry, as indicated by expression of Minichromosome Maintenance (MCM) Proteins. Materials and Methods: We used immunohistochemistry to examine the distribution of Mcm-2 in breast tissue. Power calculations based on a pilot study of 67 whole tissue sections led to selection of an independent 347-core breast carcinoma tissue microarray validation set. We tested for associations between Mcm-2 (and Ki-67) labeling index (LI) and various clinicopathologic parameters. Results: Mcm-2 was expressed more frequently than the standard proliferation marker Ki-67 in whole tissue sections of normal breast (P = .0003) and breast carcinoma (P < .0001). In 221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive association with tumor size (P = .002), mitotic index (P < .0001), histologic grade (P < .0001), and the Nottingham Prognostic Index (NPI) score (P < .0...
Libero Lauriola - One of the best experts on this subject based on the ideXlab platform.
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Minichromosome Maintenance Protein 7 and geminin expression prognostic value in laryngeal squamous cell carcinoma in patients treated with radiotherapy and cetuximab
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 2017Co-Authors: G Almadori, Libero Lauriola, Antonella Coli, Francesco Bussu, Roberto Gallus, Domenico Scannone, V Valentini, G Paludetti, Thomas E Carey, Franco O RanellettiAbstract:Background Minichromosome Maintenance Protein 7 (MCM7) is a downstream of human epidermal growth receptor (HER1) signaling. We examined MCM7, geminin, and HER1 expression in patients with laryngeal squamous cell carcinoma (SCC) treated with radiotherapy and cetuximab. Methods MCM7, geminin, and HER1 were evaluated by immunohistochemistry on 61 patients with laryngeal SCC. The follow-up (median, 32.1 months; range, 2–139 months) went from the beginning of therapy to tumor progression-free survival (PFS) and death (overall survival [OS]). Results MCM7, but not geminin, was associated only with HER1 expression, whereas no association was found with other clinicopathological characteristics. Patients with MCM7 high - geminin high and MCM7 high - geminin low tumor status had a risk of progression 3.1 times and 17.7 times greater, respectively, than patients with MCM7 low – geminin high tumor status. Tumor site, MCM7, and geminin were independent determinants of PFS, whereas MCM7 was an independent prognostic marker of OS. Conclusion MCM7-geminin tumor status may be prognostic for patients with laryngeal SCC treated with cetuximab and radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Minichromosome Maintenance Protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients
European Journal of Endocrinology, 2016Co-Authors: Antonella Coli, Domenico Scannone, Franco O Ranelletti, Guido Fadda, Sabrina Chiloiro, Laura De Marinis, Liverana Lauretti, Libero LauriolaAbstract:Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome Maintenance 7 (MCM7), a cell-cycle regulator Protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.
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Minichromosome Maintenance Protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients
European Journal of Endocrinology, 2016Co-Authors: Antonella Coli, Domenico Scannone, Franco O Ranelletti, Guido Fadda, Sabrina Chiloiro, Laura De Marinis, Liverana Lauretti, Sylvia L Asa, Libero LauriolaAbstract:BACKGROUND Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome Maintenance 7 (MCM7), a cell-cycle regulator Protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA. DESIGN AND METHODS In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated. RESULTS Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression. CONCLUSIONS Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.
Franco O Ranelletti - One of the best experts on this subject based on the ideXlab platform.
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Minichromosome Maintenance Protein 7 and geminin expression prognostic value in laryngeal squamous cell carcinoma in patients treated with radiotherapy and cetuximab
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 2017Co-Authors: G Almadori, Libero Lauriola, Antonella Coli, Francesco Bussu, Roberto Gallus, Domenico Scannone, V Valentini, G Paludetti, Thomas E Carey, Franco O RanellettiAbstract:Background Minichromosome Maintenance Protein 7 (MCM7) is a downstream of human epidermal growth receptor (HER1) signaling. We examined MCM7, geminin, and HER1 expression in patients with laryngeal squamous cell carcinoma (SCC) treated with radiotherapy and cetuximab. Methods MCM7, geminin, and HER1 were evaluated by immunohistochemistry on 61 patients with laryngeal SCC. The follow-up (median, 32.1 months; range, 2–139 months) went from the beginning of therapy to tumor progression-free survival (PFS) and death (overall survival [OS]). Results MCM7, but not geminin, was associated only with HER1 expression, whereas no association was found with other clinicopathological characteristics. Patients with MCM7 high - geminin high and MCM7 high - geminin low tumor status had a risk of progression 3.1 times and 17.7 times greater, respectively, than patients with MCM7 low – geminin high tumor status. Tumor site, MCM7, and geminin were independent determinants of PFS, whereas MCM7 was an independent prognostic marker of OS. Conclusion MCM7-geminin tumor status may be prognostic for patients with laryngeal SCC treated with cetuximab and radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Minichromosome Maintenance Protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients
European Journal of Endocrinology, 2016Co-Authors: Antonella Coli, Domenico Scannone, Franco O Ranelletti, Guido Fadda, Sabrina Chiloiro, Laura De Marinis, Liverana Lauretti, Libero LauriolaAbstract:Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome Maintenance 7 (MCM7), a cell-cycle regulator Protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.
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Minichromosome Maintenance Protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients
European Journal of Endocrinology, 2016Co-Authors: Antonella Coli, Domenico Scannone, Franco O Ranelletti, Guido Fadda, Sabrina Chiloiro, Laura De Marinis, Liverana Lauretti, Sylvia L Asa, Libero LauriolaAbstract:BACKGROUND Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome Maintenance 7 (MCM7), a cell-cycle regulator Protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA. DESIGN AND METHODS In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated. RESULTS Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression. CONCLUSIONS Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.
Okay Saydam - One of the best experts on this subject based on the ideXlab platform.
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Overexpression of Minichromosome Maintenance Protein 10 in medulloblastoma and its clinical implications
Pediatric blood & cancer, 2017Co-Authors: Daniel Senfter, Sibylle Madlener, Nurten Saydam, Erdogan Pekcan Erkan, Thomas Strobel, Erdener Özer, Gerhard Jungwirth, Marcel Kool, Okay SaydamAbstract:Background Overexpression of Minichromosome Maintenance (MCM) Proteins 2, 3, and 7 is associated with migration and invasion in medulloblastoma (MB). However, expression profiling of all prereplication complex (pre-RC) has not been addressed in MBs. Procedure We performed mRNA expression profiling of a large set of pre-RC elements in cell lines and tumor tissues of MB. RNAi technology was employed for functional studies in MB cell lines. Results Our data showed that most of the pre-RC components are significantly overexpressed in MB. Among all pre-RC mRNAs, MCM10 showed the highest level of expression (∼500- to 1,000-fold) in MB cell lines and tissues compared to the levels detected in cerebellum. In addition, RNAi silencing of MCM10 caused reduced cell proliferation and cell viability in MB cells. Conclusions Taken together, our study reveals that the pre-RC is dysregulated in MB. In addition, MCM10, a member of this complex, is significantly overexpressed in MB and is required for tumor cell proliferation.
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depletion of Minichromosome Maintenance Protein 7 inhibits glioblastoma multiforme tumor growth in vivo
Oncogene, 2014Co-Authors: Erdogan Pekcan Erkan, Grant Lewandrowski, Sibylle Madlener, Nurten Saydam, Thomas Czech, Thomas Strobel, Bakhos A Tannous, Okay SaydamAbstract:Depletion of Minichromosome Maintenance Protein 7 inhibits glioblastoma multiforme tumor growth in vivo
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Depletion of Minichromosome Maintenance Protein 7 inhibits glioblastoma multiforme tumor growth in vivo
Oncogene, 2014Co-Authors: Erdogan Pekcan Erkan, Grant Lewandrowski, Sibylle Madlener, Nurten Saydam, Thomas Czech, Thomas Strobel, B Tannous, Okay SaydamAbstract:Minichromosome Maintenance (MCM) Proteins are key elements that function as a part of the pre-replication complex to initiate DNA replication in eukaryotes. Consistent with their roles in initiating DNA replication, overexpression of MCM family members has been observed in several malignancies. Through bioinformatic analysis of The Cancer Genome Atlas’s data on glioblastoma multiforme (GBM), we found that the genomic region containing MCM7 gene was amplified in more than 80% of the present cases. To validate this finding and to identify the possible contribution of the remaining members of the MCM family to GBM progression, we used quantitative real-time PCR to analyze the gene expression profiles of all MCM family members in Grade IV (GBM) tissue samples and observed a significant upregulation in GBM samples compared with normal white matter tissues. In addition, we compared the observed gene expression profiles with those of Grade II and Grade III astrocytoma samples and determined that the observed upregulation was restricted and specific to Grade IV. MCM7 was the most upregulated gene in the gene set we analyzed, and therefore we wanted to identify the role of MCM7 in GBM progression. We determined that siRNA-mediated knockdown of MCM7 expression reduced GBM cell proliferation and also inhibited tumor growth in both xenograft and orthotopic mouse models of GBM. Taken together, our data suggest that MCM7 can be a potential prognostic marker and a novel therapeutic target in GBM therapy.
Antonella Coli - One of the best experts on this subject based on the ideXlab platform.
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Minichromosome Maintenance Protein 7 and geminin expression prognostic value in laryngeal squamous cell carcinoma in patients treated with radiotherapy and cetuximab
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 2017Co-Authors: G Almadori, Libero Lauriola, Antonella Coli, Francesco Bussu, Roberto Gallus, Domenico Scannone, V Valentini, G Paludetti, Thomas E Carey, Franco O RanellettiAbstract:Background Minichromosome Maintenance Protein 7 (MCM7) is a downstream of human epidermal growth receptor (HER1) signaling. We examined MCM7, geminin, and HER1 expression in patients with laryngeal squamous cell carcinoma (SCC) treated with radiotherapy and cetuximab. Methods MCM7, geminin, and HER1 were evaluated by immunohistochemistry on 61 patients with laryngeal SCC. The follow-up (median, 32.1 months; range, 2–139 months) went from the beginning of therapy to tumor progression-free survival (PFS) and death (overall survival [OS]). Results MCM7, but not geminin, was associated only with HER1 expression, whereas no association was found with other clinicopathological characteristics. Patients with MCM7 high - geminin high and MCM7 high - geminin low tumor status had a risk of progression 3.1 times and 17.7 times greater, respectively, than patients with MCM7 low – geminin high tumor status. Tumor site, MCM7, and geminin were independent determinants of PFS, whereas MCM7 was an independent prognostic marker of OS. Conclusion MCM7-geminin tumor status may be prognostic for patients with laryngeal SCC treated with cetuximab and radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Minichromosome Maintenance Protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients
European Journal of Endocrinology, 2016Co-Authors: Antonella Coli, Domenico Scannone, Franco O Ranelletti, Guido Fadda, Sabrina Chiloiro, Laura De Marinis, Liverana Lauretti, Libero LauriolaAbstract:Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome Maintenance 7 (MCM7), a cell-cycle regulator Protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.
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Minichromosome Maintenance Protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients
European Journal of Endocrinology, 2016Co-Authors: Antonella Coli, Domenico Scannone, Franco O Ranelletti, Guido Fadda, Sabrina Chiloiro, Laura De Marinis, Liverana Lauretti, Sylvia L Asa, Libero LauriolaAbstract:BACKGROUND Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome Maintenance 7 (MCM7), a cell-cycle regulator Protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA. DESIGN AND METHODS In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated. RESULTS Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression. CONCLUSIONS Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.