The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Mauro Papotti - One of the best experts on this subject based on the ideXlab platform.
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Large Cell Carcinoma of the lung clinically oriented classification integrating immunohistochemistry and molecular biology
Virchows Archiv, 2014Co-Authors: Giacomo Rossi, Mauro Papotti, Mc Mengoli, Alessia Cavazza, Davide Nicoli, Mattia Barbareschi, Chiara Cantaloni, A Tironi, Paolo Graziano, Massimiliano PaciAbstract:This study aimed at challenging pulmonary Large Cell Carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous Cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 Large Cell neuroendocrine Carcinomas demonstrated a true neuroendocrine Cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like Carcinomas showed squamous Cell markers. Eighteen out of 22 clear Cell Carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous Cell differentiation was present in four cases. Eighteen out of 20 Large Cell Carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenoCarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, three of which also harbored KRAS mutations. When positive and negative immunohistochemical staining for these markers was combined, three subsets of LCC emerged exhibiting glandular, squamous, and neuroendocrine differentiation. Molecular alterations were restricted to tumors classified as adenoCarcinoma. Stratifying LCC into specific categories using immunohistochemistry and molecular analysis may significantly impact on the choice of therapy.
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differential thymidylate synthase expression in different variants of Large Cell Carcinoma of the lung
Clinical Cancer Research, 2009Co-Authors: Valentina Monica, Paolo Ceppi, Luisella Righi, Marco Volante, Giorgio V. Scagliotti, A Cambieri, Marco Lo Iacono, Silvia Saviozzi, Silvia Novello, Mauro PapottiAbstract:Purpose: In non–small Cell lung cancer, higher thymidylate synthase (TS) levels have been reported in squamous Cell Carcinoma (SCC) compared with adenoCarcinoma (ADC). Data on TS expression in Large-Cell Carcinoma (LCC) are scanty. Experimental Design: TS mRNA and protein levels were analyzed in 42 surgical cases of pulmonary LCC, including 8 Large-Cell neuroendocrine Carcinomas, and were compared with controls represented by ADC ( n = 41), SCC ( n = 30), and small-Cell lung Carcinoma (SCLC; n = 33). TS levels were also correlated with the expression of Ki67 and E2F1. Moreover, the reliability of TS expression analysis was assessed in 22 matched cytologic and surgical specimens of non–small Cell lung cancer. Results: TS mRNA levels of LCC were comparable with those of control SCC, but significantly higher than those of ADC ( P P P = 0.02) in LCC immunoreactive for p63 and desmocollin3 (markers of squamous differentiation) than those expressing TTF-1 (a marker of ADC). Both E2F1 and Ki67 levels were not correlated with TS in LCCs. Finally, a linear correlation in TS protein levels was observed between matched cytologic and surgical specimens. Conclusion: The pulmonary LCC immunoprofile may resemble that of SCCs or ADCs. This immunoprofile is associated with differential TS expression levels, which may support a more appropriate therapeutic strategy decision. (Clin Cancer Res 2009;15(24):7547–52)
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Desmocollin-3: a new marker of squamous differentiation in undifferentiated Large-Cell Carcinoma of the lung.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2009Co-Authors: Valentina Monica, Paolo Ceppi, Luisella Righi, Veronica Tavaglione, Marco Volante, Giuseppe Pelosi, Giorgio V. Scagliotti, Mauro PapottiAbstract:Lung cancer classification in small-Cell and non-small-Cell types was recently challenged by data on the differential efficacy of new cytotoxic agents in specific histotypes. An accurate histotype definition has therefore gained interest in both preoperative and surgical materials, but is a hard task especially in undifferentiated Large-Cell tumors lacking morphological signs of squamous or glandular differentiation. The responsiveness of these latter subtypes to new drugs apparently more selective for adenoCarcinomas or squamous Carcinomas is not fully understood, also due to the heterogeneity of diagnostic criteria for this tumor entity. Current immunohistochemical markers are not fully specific and new molecules are to be explored. On the basis of gene expression profiling data, reporting a remarkable differential expression of desmocollin-3 (a protein localized in desmosomal junctions of stratified epithelial) between adeno- and squamous cancers, we immunostained 62 cases of resected undifferentiated Large-Cell lung Carcinomas for desmocollin-3 (and for TTF-1, p63 and mucin stain), to test its ability to identify a (residual) squamous phenotype, if present. Desmocollin-3 was expressed in almost half of the undifferentiated Large-Cell cancers and was mutually exclusive with TTF-1 (positive in 39%; the remaining 18 % of cases was double negative). Special Large-Cell Carcinoma variants expressed desmocollin-3 in 6 of 6 basaloid, 7 of 12 clear-Cell types, again mutually exclusive with TTF-1 expression. None of seven sarcomatoid Carcinomas reacted for either marker. In 31 cytological samples diagnosed as 'non-small-Cell lung Carcinoma', desmocollin-3 was again mutually exclusive with TTF-1 and stained all squamous Carcinomas, 1 of 19 adenoCarcinoma only, and 50% of Large-Cell Carcinoma (all histologically confirmed). This combined morphophenotypic approach may represent a valid adjunct (for both surgical and cytological samples) in the selection of patients with lung cancer to medical treatments tailored according to different efficacy in different lung Carcinomas of the squamous, adeno- and Large-Cell types.
Takehiko Fujisawa - One of the best experts on this subject based on the ideXlab platform.
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Imprint cytologic features of pulmonary Large Cell neuroendocrine Carcinoma: Comparison with classic Large Cell Carcinoma.
Oncology reports, 2004Co-Authors: Akira Iyoda, Kenzo Hiroshima, Masayuki Baba, Hidemi Ohwada, Hiroko Saitoh, Yasumitsu Moriya, Kiyoshi Shibuya, Toshihiko Iizasa, Fumio Horiuchi, Takehiko FujisawaAbstract:The World Health Organization (WHO) categorized Large Cell neuroendocrine Carcinoma (LCNEC) as a variant of Large Cell Carcinoma in 1999. However, cytologic features of these tumors have not yet been adequately characterized. The cytologic features of 24 cases of LCNEC were analyzed and compared to the features of 16 cases of classic Large Cell Carcinoma (CLCC). Giant Cells, neutrophils and cytophagocytosis were observed more frequently in CLCC than in LCNEC (p
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Pulmonary Large Cell Carcinoma with Rhabdoid Phenotype
Ultrastructural pathology, 2003Co-Authors: Kenzo Hiroshima, Akira Iyoda, Tetsuya Toyozaki, Yukiko Haga, Hidemi Ohwada, Kiyoshi Shibuya, Toshihiko Iizasa, Fumihiko Shimamura, Yasuo Sekine, Takehiko FujisawaAbstract:A 70-year-old woman presented with a coin lesion in her left lung. The tumor was well circumscribed and had a Large area of central necrosis with a thin rim of viable tumor Cells. It showed a solid growth pattern of polygonal Cells with eosinophilic intracytoplasmic inclusion bodies. Immunohistochemically, the tumor Cells were positive for vimentin, neural Cell adhesion molecule, neuron-specific enolase, and vascular endothelial growth factor. Electron microscopy revealed intracytoplasmic inclusion bodies consisting of whorled intermediate filaments. Based on histological and immunohistochemical findings, the patient was diagnosed as having pulmonary Large Cell Carcinoma with rhabdoid phenotype (LCCRP). The patient was in stage IA, and the histological findings may be the prototype of pure LCCRP. The tumor recurred after 6 years, and the second tumor had more apparent intracytoplasmic inclusion bodies. It is worthwhile detecting and recognizing the significance of these intracytoplasmic inclusions because...
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Adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features
Cancer, 2001Co-Authors: Akira Iyoda, Kenzo Hiroshima, Tetsuya Toyozaki, Yukiko Haga, Masayuki Baba, Takehiko Fujisawa, Hidemi OhwadaAbstract:In 1999, the World Health Organization categorized Large Cell neuroendocrine Carcinoma, Large Cell Carcinoma with neuroendocrine differentiation, and Large Cell Carcinoma with neuroendocrine morphology as a variant of Large Cell Carcinoma. Patients with Large Cell Carcinoma with neuroendocrine features have poor prognoses, comparable to those for small Cell lung Carcinoma. Small Cell lung Carcinoma is sensitive to chemotherapy; however, it is still unclear whether Large Cell Carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. The authors analyzed 73 patients with Large Cell Carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features. In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small Cell lung Carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with Large Cell Carcinoma with neuroendocrine features in early stage. Copyright 2001 American Cancer Society.
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Adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features
Cancer, 2001Co-Authors: Akira Iyoda, Kenzo Hiroshima, Tetsuya Toyozaki, Yukiko Haga, Masayuki Baba, Takehiko Fujisawa, Hidemi OhwadaAbstract:BACKGROUND In 1999, the World Health Organization categorized Large Cell neuroendocrine Carcinoma, Large Cell Carcinoma with neuroendocrine differentiation, and Large Cell Carcinoma with neuroendocrine morphology as a variant of Large Cell Carcinoma. Patients with Large Cell Carcinoma with neuroendocrine features have poor prognoses, comparable to those for small Cell lung Carcinoma. Small Cell lung Carcinoma is sensitive to chemotherapy; however, it is still unclear whether Large Cell Carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. METHODS The authors analyzed 73 patients with Large Cell Carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features. RESULTS In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small Cell lung Carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. CONCLUSIONS Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with Large Cell Carcinoma with neuroendocrine features in early stage. Cancer 2001;92:1108–12. © 2001 American Cancer Society.
Lynette M. Sholl - One of the best experts on this subject based on the ideXlab platform.
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Large-Cell Carcinoma of the lung: a diagnostic category redefined by immunohistochemistry and genomics.
Current opinion in pulmonary medicine, 2014Co-Authors: Lynette M. ShollAbstract:PURPOSE OF REVIEW The current classification system defines Large-Cell Carcinoma (LCC) morphologically as an undifferentiated lung Carcinoma lacking features of adenoCarcinoma (ADC), squamous Cell, or small-Cell Carcinoma. As a result, LCC has evolved into a clinicopathologically heterogeneous entity. In the current era of histology-driven predictive molecular testing and oncologic management, ambiguous diagnostic categories frustrate attempts to provide more personalized cancer care, thus the pathology community has engaged in a concerted effort to revise the criteria for LCC. RECENT FINDINGS Most cases of LCC are immunophenotypically similar to ADC or squamous Cell Carcinoma. LCC lacking squamous and neuroendocrine features is clinically and genomically indistinguishable from solid ADC. Even cases of LCC lacking immunophenotypic differentiation may contain genomic alterations characteristic of other forms of lung Carcinoma. SUMMARY Applying ancillary techniques, most cases of LCC can be reclassified into more informative categories that may guide molecular testing for predictive biomarkers and enable selection of more appropriate therapies.
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Pulmonary Large Cell Carcinoma lacking squamous differentiation is clinicopathologically indistinguishable from solid-subtype adenoCarcinoma
Archives of pathology & laboratory medicine, 2013Co-Authors: David H. Hwang, David Szeto, Anthony S. Perry, Jacqueline L. Bruce, Lynette M. ShollAbstract:Context.— Pulmonary Large Cell Carcinoma (LCC) includes tumors not readily diagnosed as adenoCarcinoma (ADC) or squamous Cell Carcinoma on morphologic grounds, without regard to immunophenotype, ac...
Valentina Monica - One of the best experts on this subject based on the ideXlab platform.
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differential thymidylate synthase expression in different variants of Large Cell Carcinoma of the lung
Clinical Cancer Research, 2009Co-Authors: Valentina Monica, Paolo Ceppi, Luisella Righi, Marco Volante, Giorgio V. Scagliotti, A Cambieri, Marco Lo Iacono, Silvia Saviozzi, Silvia Novello, Mauro PapottiAbstract:Purpose: In non–small Cell lung cancer, higher thymidylate synthase (TS) levels have been reported in squamous Cell Carcinoma (SCC) compared with adenoCarcinoma (ADC). Data on TS expression in Large-Cell Carcinoma (LCC) are scanty. Experimental Design: TS mRNA and protein levels were analyzed in 42 surgical cases of pulmonary LCC, including 8 Large-Cell neuroendocrine Carcinomas, and were compared with controls represented by ADC ( n = 41), SCC ( n = 30), and small-Cell lung Carcinoma (SCLC; n = 33). TS levels were also correlated with the expression of Ki67 and E2F1. Moreover, the reliability of TS expression analysis was assessed in 22 matched cytologic and surgical specimens of non–small Cell lung cancer. Results: TS mRNA levels of LCC were comparable with those of control SCC, but significantly higher than those of ADC ( P P P = 0.02) in LCC immunoreactive for p63 and desmocollin3 (markers of squamous differentiation) than those expressing TTF-1 (a marker of ADC). Both E2F1 and Ki67 levels were not correlated with TS in LCCs. Finally, a linear correlation in TS protein levels was observed between matched cytologic and surgical specimens. Conclusion: The pulmonary LCC immunoprofile may resemble that of SCCs or ADCs. This immunoprofile is associated with differential TS expression levels, which may support a more appropriate therapeutic strategy decision. (Clin Cancer Res 2009;15(24):7547–52)
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Desmocollin-3: a new marker of squamous differentiation in undifferentiated Large-Cell Carcinoma of the lung.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2009Co-Authors: Valentina Monica, Paolo Ceppi, Luisella Righi, Veronica Tavaglione, Marco Volante, Giuseppe Pelosi, Giorgio V. Scagliotti, Mauro PapottiAbstract:Lung cancer classification in small-Cell and non-small-Cell types was recently challenged by data on the differential efficacy of new cytotoxic agents in specific histotypes. An accurate histotype definition has therefore gained interest in both preoperative and surgical materials, but is a hard task especially in undifferentiated Large-Cell tumors lacking morphological signs of squamous or glandular differentiation. The responsiveness of these latter subtypes to new drugs apparently more selective for adenoCarcinomas or squamous Carcinomas is not fully understood, also due to the heterogeneity of diagnostic criteria for this tumor entity. Current immunohistochemical markers are not fully specific and new molecules are to be explored. On the basis of gene expression profiling data, reporting a remarkable differential expression of desmocollin-3 (a protein localized in desmosomal junctions of stratified epithelial) between adeno- and squamous cancers, we immunostained 62 cases of resected undifferentiated Large-Cell lung Carcinomas for desmocollin-3 (and for TTF-1, p63 and mucin stain), to test its ability to identify a (residual) squamous phenotype, if present. Desmocollin-3 was expressed in almost half of the undifferentiated Large-Cell cancers and was mutually exclusive with TTF-1 (positive in 39%; the remaining 18 % of cases was double negative). Special Large-Cell Carcinoma variants expressed desmocollin-3 in 6 of 6 basaloid, 7 of 12 clear-Cell types, again mutually exclusive with TTF-1 expression. None of seven sarcomatoid Carcinomas reacted for either marker. In 31 cytological samples diagnosed as 'non-small-Cell lung Carcinoma', desmocollin-3 was again mutually exclusive with TTF-1 and stained all squamous Carcinomas, 1 of 19 adenoCarcinoma only, and 50% of Large-Cell Carcinoma (all histologically confirmed). This combined morphophenotypic approach may represent a valid adjunct (for both surgical and cytological samples) in the selection of patients with lung cancer to medical treatments tailored according to different efficacy in different lung Carcinomas of the squamous, adeno- and Large-Cell types.
Akira Iyoda - One of the best experts on this subject based on the ideXlab platform.
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Imprint cytologic features of pulmonary Large Cell neuroendocrine Carcinoma: Comparison with classic Large Cell Carcinoma.
Oncology reports, 2004Co-Authors: Akira Iyoda, Kenzo Hiroshima, Masayuki Baba, Hidemi Ohwada, Hiroko Saitoh, Yasumitsu Moriya, Kiyoshi Shibuya, Toshihiko Iizasa, Fumio Horiuchi, Takehiko FujisawaAbstract:The World Health Organization (WHO) categorized Large Cell neuroendocrine Carcinoma (LCNEC) as a variant of Large Cell Carcinoma in 1999. However, cytologic features of these tumors have not yet been adequately characterized. The cytologic features of 24 cases of LCNEC were analyzed and compared to the features of 16 cases of classic Large Cell Carcinoma (CLCC). Giant Cells, neutrophils and cytophagocytosis were observed more frequently in CLCC than in LCNEC (p
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Pulmonary Large Cell Carcinoma with Rhabdoid Phenotype
Ultrastructural pathology, 2003Co-Authors: Kenzo Hiroshima, Akira Iyoda, Tetsuya Toyozaki, Yukiko Haga, Hidemi Ohwada, Kiyoshi Shibuya, Toshihiko Iizasa, Fumihiko Shimamura, Yasuo Sekine, Takehiko FujisawaAbstract:A 70-year-old woman presented with a coin lesion in her left lung. The tumor was well circumscribed and had a Large area of central necrosis with a thin rim of viable tumor Cells. It showed a solid growth pattern of polygonal Cells with eosinophilic intracytoplasmic inclusion bodies. Immunohistochemically, the tumor Cells were positive for vimentin, neural Cell adhesion molecule, neuron-specific enolase, and vascular endothelial growth factor. Electron microscopy revealed intracytoplasmic inclusion bodies consisting of whorled intermediate filaments. Based on histological and immunohistochemical findings, the patient was diagnosed as having pulmonary Large Cell Carcinoma with rhabdoid phenotype (LCCRP). The patient was in stage IA, and the histological findings may be the prototype of pure LCCRP. The tumor recurred after 6 years, and the second tumor had more apparent intracytoplasmic inclusion bodies. It is worthwhile detecting and recognizing the significance of these intracytoplasmic inclusions because...
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Adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features
Cancer, 2001Co-Authors: Akira Iyoda, Kenzo Hiroshima, Tetsuya Toyozaki, Yukiko Haga, Masayuki Baba, Takehiko Fujisawa, Hidemi OhwadaAbstract:In 1999, the World Health Organization categorized Large Cell neuroendocrine Carcinoma, Large Cell Carcinoma with neuroendocrine differentiation, and Large Cell Carcinoma with neuroendocrine morphology as a variant of Large Cell Carcinoma. Patients with Large Cell Carcinoma with neuroendocrine features have poor prognoses, comparable to those for small Cell lung Carcinoma. Small Cell lung Carcinoma is sensitive to chemotherapy; however, it is still unclear whether Large Cell Carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. The authors analyzed 73 patients with Large Cell Carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features. In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small Cell lung Carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with Large Cell Carcinoma with neuroendocrine features in early stage. Copyright 2001 American Cancer Society.
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Adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features
Cancer, 2001Co-Authors: Akira Iyoda, Kenzo Hiroshima, Tetsuya Toyozaki, Yukiko Haga, Masayuki Baba, Takehiko Fujisawa, Hidemi OhwadaAbstract:BACKGROUND In 1999, the World Health Organization categorized Large Cell neuroendocrine Carcinoma, Large Cell Carcinoma with neuroendocrine differentiation, and Large Cell Carcinoma with neuroendocrine morphology as a variant of Large Cell Carcinoma. Patients with Large Cell Carcinoma with neuroendocrine features have poor prognoses, comparable to those for small Cell lung Carcinoma. Small Cell lung Carcinoma is sensitive to chemotherapy; however, it is still unclear whether Large Cell Carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. METHODS The authors analyzed 73 patients with Large Cell Carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for Large Cell Carcinoma with neuroendocrine features. RESULTS In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small Cell lung Carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. CONCLUSIONS Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with Large Cell Carcinoma with neuroendocrine features in early stage. Cancer 2001;92:1108–12. © 2001 American Cancer Society.
