Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma: A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy

Yugo Tanaka, Hiroyuki Ogawa, Kazuya Uchino, Chiho Ohbayashi, Yoshimasa Maniwa, Wataru Nishio, Atsunori Nakao, Masahiro Yoshimura

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume145
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

Fingerprint

Neuroendocrine Carcinoma
Large Cell Carcinoma
Neuroendocrine Tumors
Staining and Labeling
Drug Therapy
Lung
Survival
Neoplasms
Survival Rate
Neural Cell Adhesion Molecules
Chromogranin A
Synaptophysin
Multivariate Analysis
Confidence Intervals

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma : A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy. / Tanaka, Yugo; Ogawa, Hiroyuki; Uchino, Kazuya; Ohbayashi, Chiho; Maniwa, Yoshimasa; Nishio, Wataru; Nakao, Atsunori; Yoshimura, Masahiro.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 145, No. 3, 03.2013, p. 839-846.

Research output: Contribution to journalArticle

Tanaka, Yugo ; Ogawa, Hiroyuki ; Uchino, Kazuya ; Ohbayashi, Chiho ; Maniwa, Yoshimasa ; Nishio, Wataru ; Nakao, Atsunori ; Yoshimura, Masahiro. / Immunohistochemical studies of pulmonary large cell neuroendocrine carcinoma : A possible association between staining patterns with neuroendocrine markers and tumor response to chemotherapy. In: Journal of Thoracic and Cardiovascular Surgery. 2013 ; Vol. 145, No. 3. pp. 839-846.
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AU - Tanaka, Yugo

AU - Ogawa, Hiroyuki

AU - Uchino, Kazuya

AU - Ohbayashi, Chiho

AU - Maniwa, Yoshimasa

AU - Nishio, Wataru

AU - Nakao, Atsunori

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N2 - 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.

AB - 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.

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