Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma: A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy
Objective Pulmonary large cell neuroendocrine carcinoma is a rare high-grade malignant tumor. Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of...
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| Veröffentlicht in: | The Journal of thoracic and cardiovascular surgery 2013-03, Vol.145 (3), p.839-846 |
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| creator | Tanaka, Yugo, MD Ogawa, Hiroyuki, MD Uchino, Kazuya, MD Ohbayashi, Chiho, MD Maniwa, Yoshimasa, MD Nishio, Wataru, MD Nakao, Atsunori, MD Yoshimura, Masahiro, MD |
| description | Objective Pulmonary large cell neuroendocrine carcinoma is a rare high-grade malignant tumor. Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of perioperative chemotherapy in treating large cell neuroendocrine carcinoma, pathologic stage, and immunoreactivity to neuroendocrine markers. Methods A total of 63 patients with pulmonary large cell neuroendocrine carcinoma undergoing surgical resection from 2001 to 2009 were included. The resected tumors were immunohistochemically stained with the 3 neuroendocrine markers synaptophysin, chromogranin A, and neural cell adhesion molecule. We categorized patients who were positive for all 3 markers as the triple-positive group and those who were negative for 1 or 2 markers as the non–triple-positive group. Results Perioperative chemotherapy resulted in better overall survival than surgery alone ( P = .042). Multivariate analysis of survival revealed that perioperative chemotherapy was a significant independent prognostic factor (hazard ratio, 0.323; 95% confidence interval, 0.112-0.934; P = .0371). Among the patients who received perioperative chemotherapy, the non–triple-positive group had a significantly greater 5-year survival rate than the triple-positive group ( P = .0216). Moreover, among the non–triple-positive group, a significantly greater 5-year survival rate was observed for the patients who underwent surgery with chemotherapy than for those who underwent surgery without chemotherapy ( P = .0081). In contrast, no difference was found in 5-year survival between patients with chemotherapy and those without chemotherapy when the tumors were triple positive. Conclusions Our results suggest that perioperative chemotherapy might benefit the survival of patients with pulmonary large cell neuroendocrine carcinoma, in particular when the tumors are not immunoreactive to all 3 neuroendocrine markers. |
| doi_str_mv | 10.1016/j.jtcvs.2012.03.036 |
| format | Article |
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Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of perioperative chemotherapy in treating large cell neuroendocrine carcinoma, pathologic stage, and immunoreactivity to neuroendocrine markers. Methods A total of 63 patients with pulmonary large cell neuroendocrine carcinoma undergoing surgical resection from 2001 to 2009 were included. The resected tumors were immunohistochemically stained with the 3 neuroendocrine markers synaptophysin, chromogranin A, and neural cell adhesion molecule. We categorized patients who were positive for all 3 markers as the triple-positive group and those who were negative for 1 or 2 markers as the non–triple-positive group. Results Perioperative chemotherapy resulted in better overall survival than surgery alone ( P = .042). Multivariate analysis of survival revealed that perioperative chemotherapy was a significant independent prognostic factor (hazard ratio, 0.323; 95% confidence interval, 0.112-0.934; P = .0371). Among the patients who received perioperative chemotherapy, the non–triple-positive group had a significantly greater 5-year survival rate than the triple-positive group ( P = .0216). Moreover, among the non–triple-positive group, a significantly greater 5-year survival rate was observed for the patients who underwent surgery with chemotherapy than for those who underwent surgery without chemotherapy ( P = .0081). In contrast, no difference was found in 5-year survival between patients with chemotherapy and those without chemotherapy when the tumors were triple positive. Conclusions Our results suggest that perioperative chemotherapy might benefit the survival of patients with pulmonary large cell neuroendocrine carcinoma, in particular when the tumors are not immunoreactive to all 3 neuroendocrine markers.</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/j.jtcvs.2012.03.036</identifier><identifier>PMID: 22498090</identifier><language>eng</language><publisher>United States: Mosby, Inc</publisher><subject>Aged ; Antineoplastic Agents - therapeutic use ; Biomarkers, Tumor - analysis ; Carcinoma, Large Cell - drug therapy ; Carcinoma, Large Cell - pathology ; Carcinoma, Large Cell - surgery ; Carcinoma, Neuroendocrine - drug therapy ; Carcinoma, Neuroendocrine - pathology ; Carcinoma, Neuroendocrine - surgery ; Cardiothoracic Surgery ; Chromogranin A ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry - methods ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Lung Neoplasms - surgery ; Male ; Middle Aged ; Neoplasm Staging ; Neural Cell Adhesion Molecules ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Synaptophysin ; Treatment Outcome</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2013-03, Vol.145 (3), p.839-846</ispartof><rights>The American Association for Thoracic Surgery</rights><rights>2013 The American Association for Thoracic Surgery</rights><rights>Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-2f2cc352d4c4059f5aca64d8fc97e14c11f5157ccdaced12c07b3574b7d078413</citedby><cites>FETCH-LOGICAL-c459t-2f2cc352d4c4059f5aca64d8fc97e14c11f5157ccdaced12c07b3574b7d078413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jtcvs.2012.03.036$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22498090$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanaka, Yugo, MD</creatorcontrib><creatorcontrib>Ogawa, Hiroyuki, MD</creatorcontrib><creatorcontrib>Uchino, Kazuya, MD</creatorcontrib><creatorcontrib>Ohbayashi, Chiho, MD</creatorcontrib><creatorcontrib>Maniwa, Yoshimasa, MD</creatorcontrib><creatorcontrib>Nishio, Wataru, MD</creatorcontrib><creatorcontrib>Nakao, Atsunori, MD</creatorcontrib><creatorcontrib>Yoshimura, Masahiro, MD</creatorcontrib><title>Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma: A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>Objective Pulmonary large cell neuroendocrine carcinoma is a rare high-grade malignant tumor. Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of perioperative chemotherapy in treating large cell neuroendocrine carcinoma, pathologic stage, and immunoreactivity to neuroendocrine markers. Methods A total of 63 patients with pulmonary large cell neuroendocrine carcinoma undergoing surgical resection from 2001 to 2009 were included. The resected tumors were immunohistochemically stained with the 3 neuroendocrine markers synaptophysin, chromogranin A, and neural cell adhesion molecule. We categorized patients who were positive for all 3 markers as the triple-positive group and those who were negative for 1 or 2 markers as the non–triple-positive group. Results Perioperative chemotherapy resulted in better overall survival than surgery alone ( P = .042). Multivariate analysis of survival revealed that perioperative chemotherapy was a significant independent prognostic factor (hazard ratio, 0.323; 95% confidence interval, 0.112-0.934; P = .0371). Among the patients who received perioperative chemotherapy, the non–triple-positive group had a significantly greater 5-year survival rate than the triple-positive group ( P = .0216). Moreover, among the non–triple-positive group, a significantly greater 5-year survival rate was observed for the patients who underwent surgery with chemotherapy than for those who underwent surgery without chemotherapy ( P = .0081). In contrast, no difference was found in 5-year survival between patients with chemotherapy and those without chemotherapy when the tumors were triple positive. Conclusions Our results suggest that perioperative chemotherapy might benefit the survival of patients with pulmonary large cell neuroendocrine carcinoma, in particular when the tumors are not immunoreactive to all 3 neuroendocrine markers.</description><subject>Aged</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Carcinoma, Large Cell - drug therapy</subject><subject>Carcinoma, Large Cell - pathology</subject><subject>Carcinoma, Large Cell - surgery</subject><subject>Carcinoma, Neuroendocrine - drug therapy</subject><subject>Carcinoma, Neuroendocrine - pathology</subject><subject>Carcinoma, Neuroendocrine - surgery</subject><subject>Cardiothoracic Surgery</subject><subject>Chromogranin A</subject><subject>Combined Modality Therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - surgery</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Neural Cell Adhesion Molecules</subject><subject>Proportional Hazards Models</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Synaptophysin</subject><subject>Treatment Outcome</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2LFDEQbURx19VfIEiOXmaspDvT3YLCsvixsOBBBW8hU129k9nupE2ld5kf538z7awe9iIUBMJ7r6req6J4KWEtQW7e7Nf7hLe8ViDVGspcm0fFqYS2Xm0a_eNxcQqg1EorVZ4Uz5j3AFCDbJ8WJ0pVbQMtnBa_Lsdx9mHnOAXc0ejQDoLT3DliEXoxzcMYvI0HMdh4TQJpGISnOQbyXcDofP6zEZ0Po30rzsUUmN12IGGZAzqbXPBiS-mOyGdh67zz12KyKVH0LO5c2j3UG228ocjC-k6keQxRROIpeCaRglimDGlH0U6H58WT3g5ML-7fs-L7xw_fLj6vrr58urw4v1phpdu0Ur1CLLXqKqxAt722aDdV1_TY1iQrlLLXUteInUXqpEKot6Wuq23dQd1UsjwrXh91pxh-zsTJjI4XK6ynMLORqmnaVmmpMrQ8QjFmJyL1Zooub3QwEsySm9mbP7mZJTcDZa5NZr26bzBvR-r-cf4GlQHvjgDKa946iobRkc_jukiYTBfcfxq8f8DHIUeR076hA_E-zNFnB400nDnm63I6y-VIBVBqCeVvwp3Gkg</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Tanaka, Yugo, MD</creator><creator>Ogawa, Hiroyuki, MD</creator><creator>Uchino, Kazuya, MD</creator><creator>Ohbayashi, Chiho, MD</creator><creator>Maniwa, Yoshimasa, MD</creator><creator>Nishio, Wataru, MD</creator><creator>Nakao, Atsunori, MD</creator><creator>Yoshimura, Masahiro, MD</creator><general>Mosby, Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130301</creationdate><title>Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma: A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy</title><author>Tanaka, Yugo, MD ; Ogawa, Hiroyuki, MD ; Uchino, Kazuya, MD ; Ohbayashi, Chiho, MD ; Maniwa, Yoshimasa, MD ; Nishio, Wataru, MD ; Nakao, Atsunori, MD ; Yoshimura, Masahiro, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-2f2cc352d4c4059f5aca64d8fc97e14c11f5157ccdaced12c07b3574b7d078413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Carcinoma, Large Cell - drug therapy</topic><topic>Carcinoma, Large Cell - pathology</topic><topic>Carcinoma, Large Cell - surgery</topic><topic>Carcinoma, Neuroendocrine - drug therapy</topic><topic>Carcinoma, Neuroendocrine - pathology</topic><topic>Carcinoma, Neuroendocrine - surgery</topic><topic>Cardiothoracic Surgery</topic><topic>Chromogranin A</topic><topic>Combined Modality Therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - surgery</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Neural Cell Adhesion Molecules</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Synaptophysin</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tanaka, Yugo, MD</creatorcontrib><creatorcontrib>Ogawa, Hiroyuki, MD</creatorcontrib><creatorcontrib>Uchino, Kazuya, MD</creatorcontrib><creatorcontrib>Ohbayashi, Chiho, MD</creatorcontrib><creatorcontrib>Maniwa, Yoshimasa, MD</creatorcontrib><creatorcontrib>Nishio, Wataru, MD</creatorcontrib><creatorcontrib>Nakao, Atsunori, MD</creatorcontrib><creatorcontrib>Yoshimura, Masahiro, MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanaka, Yugo, MD</au><au>Ogawa, Hiroyuki, MD</au><au>Uchino, Kazuya, MD</au><au>Ohbayashi, Chiho, MD</au><au>Maniwa, Yoshimasa, MD</au><au>Nishio, Wataru, MD</au><au>Nakao, Atsunori, MD</au><au>Yoshimura, Masahiro, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma: A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>145</volume><issue>3</issue><spage>839</spage><epage>846</epage><pages>839-846</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><abstract>Objective Pulmonary large cell neuroendocrine carcinoma is a rare high-grade malignant tumor. Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of perioperative chemotherapy in treating large cell neuroendocrine carcinoma, pathologic stage, and immunoreactivity to neuroendocrine markers. Methods A total of 63 patients with pulmonary large cell neuroendocrine carcinoma undergoing surgical resection from 2001 to 2009 were included. The resected tumors were immunohistochemically stained with the 3 neuroendocrine markers synaptophysin, chromogranin A, and neural cell adhesion molecule. We categorized patients who were positive for all 3 markers as the triple-positive group and those who were negative for 1 or 2 markers as the non–triple-positive group. Results Perioperative chemotherapy resulted in better overall survival than surgery alone ( P = .042). Multivariate analysis of survival revealed that perioperative chemotherapy was a significant independent prognostic factor (hazard ratio, 0.323; 95% confidence interval, 0.112-0.934; P = .0371). Among the patients who received perioperative chemotherapy, the non–triple-positive group had a significantly greater 5-year survival rate than the triple-positive group ( P = .0216). Moreover, among the non–triple-positive group, a significantly greater 5-year survival rate was observed for the patients who underwent surgery with chemotherapy than for those who underwent surgery without chemotherapy ( P = .0081). In contrast, no difference was found in 5-year survival between patients with chemotherapy and those without chemotherapy when the tumors were triple positive. Conclusions Our results suggest that perioperative chemotherapy might benefit the survival of patients with pulmonary large cell neuroendocrine carcinoma, in particular when the tumors are not immunoreactive to all 3 neuroendocrine markers.</abstract><cop>United States</cop><pub>Mosby, Inc</pub><pmid>22498090</pmid><doi>10.1016/j.jtcvs.2012.03.036</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Antineoplastic Agents - therapeutic use Biomarkers, Tumor - analysis Carcinoma, Large Cell - drug therapy Carcinoma, Large Cell - pathology Carcinoma, Large Cell - surgery Carcinoma, Neuroendocrine - drug therapy Carcinoma, Neuroendocrine - pathology Carcinoma, Neuroendocrine - surgery Cardiothoracic Surgery Chromogranin A Combined Modality Therapy Female Humans Immunohistochemistry - methods Lung Neoplasms - drug therapy Lung Neoplasms - pathology Lung Neoplasms - surgery Male Middle Aged Neoplasm Staging Neural Cell Adhesion Molecules Proportional Hazards Models Retrospective Studies Survival Rate Synaptophysin Treatment Outcome |
| title | Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma: A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy |
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