Prognostic factors in neuroendocrine lung tumors: a Spanish multicenter study

Garcı́a-Yuste, Mariano; Matilla, José-María; Alvarez-Gago, T.; Duque, J.L.; Heras, F.; Cerezal, Luis; Ramos, Guillermo

doi:10.1016/s0003-4975(00)01369-2

Cited by 141 publications

(28 citation statements)

References 16 publications

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“…The latter ranges from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), to high-grade small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) (1,2), and the 5-year survival rates for TC, AC, LCNEC, and SCLC were 87, 56, 27, and 9%, respectively (2). Similar results were also reported by Garcia-Yuste et al, and the 5-year survival rates for TC, AC, LCENC, and SCLC were 96, 72, 21, and 14%, respectively (3). These results show that both SCLC and LCNEC are highly malignant and have a similar poor prognosis.…”

Section: Introductionsupporting

confidence: 75%

Anti-HuC and -HuD autoantibodies are differential sero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung

Matsumoto

Ryuge

Kobayashi³

et al. 2012

Int J Oncol

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Abstract. Aiming to identify novel sero-diagnostic markers for neu ro endo c r i ne ca rci nom a s of t he lu ng, t he two-dimensional gel electrophoresis-immunoblot method was used to analyze tumor-associated autoantibodies in patients with small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Several autoantigens were revealed and anti-HuC autoantibody was detected only in sera of SCLC patients. Since Hu family proteins including HuC are well-known causes of paraneoplastic encephalomyelitis/ sensory neuronopathy (PEM/SN), the expression of HuC as well as HuD mRNAs and their proteins was studied in 11 lung cancer cell lines. The expression of HuC and HuD mRNAs and proteins was only detected in SCLC-and LCNECderived cells. To validate the existence of anti-HuC and -HuD auto-antibodies, we studied a large number of sera including those from lung cancer patients employing dot blot analysis. Anti-HuC and -HuD autoantibodies were detected only in SCLC cases with or without PEM/SN, and not in the sera of LCNEC patients. The mechanism leading to different anti-HuC and -HuD autoantibody production between SCLC and LCNEC is unclear; however, the results from the present and previous studies suggest that anti-HuC and -HuD autoantibodies are novel differential sero-diagnostic markers for SCLC from LCNEC. IntroductionLung cancer is the leading cause of cancer-related death worldwide. Based on the presence or absence of cellular neuroendo crine differentiation, lung cancer can be grouped into non-neuroendocrine or neuroendocrine tumors. The former is roughly equal to the non-small cell lung cancer (NSCLC) largely comprising squamous cell carcinoma (SCC) and adenocarcinoma (AD). The latter ranges from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), to high-grade small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) (1,2), and the 5-year survival rates for TC, AC, LCNEC, and SCLC were 87, 56, 27, and 9%, respectively (2). Similar results were also reported by Garcia-Yuste et al, and the 5-year survival rates for TC, AC, LCENC, and SCLC were 96, 72, 21, and 14%, respectively (3). These results show that both SCLC and LCNEC are highly malignant and have a similar poor prognosis. Pro-gastrin-releasing peptide (pro-GRP) is a well-known sero-diagnostic marker for SCLC; however, its positive rate is lower in stage I and II (35-45%) than in stage III (55-70%) and IV (70-80%). At present, no specific sero-diagnostic markers for distinguishing SCLC from LCNEC have been reported.Autoantibodies are antibodies detected in the sera of patients with various autoimmune diseases. They are also frequently observed in the sera of patients with various malignancies even in the early stages, and, thus, the possibilities for them to be used as potential tumor markers have been suggested (4-10). Hanash (11) has described that harnessing the immune response to identify novel cancer biomarkers is an attractive strategy, because the immune system performs biological ...

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Section: Introductionsupporting

confidence: 75%

Anti-HuC and -HuD autoantibodies are differential sero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung

Matsumoto

Ryuge

Kobayashi³

et al. 2012

Int J Oncol

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“…31,32 We observed a 24% 5-year overall survival rate and a 31-month median survival in patients with poorly differentiated LCNEC patients, in line with previous studies that demonstrated a 5-year survival rate between 13% and 57%. 3,8,9,11,22,27,28 In the current study, a high mitotic count and a low number of neuroendocrine markers at immunohistochemistry emerged as prognostic factors for survival in patients with poorly differentiated LCNEC. For the first time, we have identified relevant prognostic impact for the mitotic count in poorly differentiated LCNEC: Patients with < 37 mitoses per 10 HPFs had tumors that were characterized by a less aggressive behavior.…”

Section: Discussionmentioning

confidence: 56%

“…[15][16][17][18][19][20][21] Previous studies suggested several distinctive clinical features of LCNEC compared with well-differentiated NEC, including: tobacco use, male gender, advanced stage at presentation, and more frequent peripheral presentation. 10,11,13,[22][23][24] Historic LCNEC series have suggested a natural aggressive course with a median survival < 1 year. 25,26 From a prognostic standpoint, LCNEC stage has been described as a major determinant for survival in most studies [27][28][29] but not in all studies.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas

Faggiano

Sabourin

Ducreux

et al. 2007

Cancer

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BACKGROUND.Poorly differentiated large cell neuroendocrine carcinomas (LCNEC) comprise a rare and still scarcely known subgroup of neuroendocrine tumors. The objective of this study was to investigate the epidemiology, clinical presentation, prognostic factors, and molecular pathways of patients with poorly differentiated LCNEC.METHODS.Forty‐one patients who had a confirmed diagnosis of poorly differentiated LCNEC according to the criteria of the most recent World Health Organization classification of neuroendocrine tumors of the lung entered the study. The clinicopathologic features of patients with poorly differentiated LCNEC were reviewed, prognostic parameters for their survival were studied, and the prognostic roles of the proteins involved in cell cycle regulation were investigated with tissue array analysis in a subset of patients with LCNEC.RESULTS.Twenty‐four men and 17 women with a median age of 63 years (age range, 26–81 years) who had LCNEC were studied. LCNEC developed after therapy for a first cancer in 14% of patients. Neither a personal or familial history of endocrine tumors nor a primary association that was compatible with an inherited syndrome was observed. The increase of at least 1 serum biologic marker was observed in 93% of patients. A primary tumor was identified in only 63% patients. Thirty‐one patients had distant metastases, and 10 patients had only lymph node metastases at the time of the diagnosis. The 5‐year survival rate was 24%. High mitotic count, low expression of neuroendocrine markers, and a Bcl‐2/Bax ratio > 1 were unfavorable prognostic factors for survival (P < .01). All patients who had isolated peripheral lymph node LCNEC achieved a cure.CONCLUSIONS.The results from this study highlighted distinctive clinical features and prognostic indicators of poorly differentiated LCNEC. Peripheral isolated lymph node clinical presentation is proposed as a new clinical entity. Cancer 2007. © 2007 American Cancer Society.

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“…Introduction of somatostatin analogues during the metastatic phase of the disease has improved the management of carcinoid syndrome, but as yet, there has been no demonstration of its real impact on tumour growth or a possible impact on survival [6,7,8,9,10,11,12,13,14]. Systemic chemotherapy is often ineffective in the case of well-differentiated metastatic tumours, but may be considered in selected cases, such as those showing rapidly growing disease after less toxic treatments [15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Carcinoid Tumours: Indolent but Not Benign

Dosso¹,

Bajetta²,

Procopio³

et al. 2007

Oncology

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Background: The aim of this retrospective study was to analyse the malignant behaviour of low-grade pulmonary neuroendocrine tumours (NETs) treated at our institution. Patients and Methods: We reviewed 48 consecutive patients with pulmonary NETs referred to our Medical Oncology Unit between 1998 and 2006, including 33 subjects with typical carcinoids (TCs) and 15 with atypical carcinoids (ACs). Results: At diagnosis, there were 37 metastatic and 11 non-metastatic patients. Medical treatments used were somatostatin analogues, combined chemotherapy, within study protocols, 5-fluorouracil/dacarbazine/epiadriamycin (FDE), and oxaliplatin plus capecitabine (XELOX). Median disease-free survival was 72 months for the TC patients and 38 months for the AC patients. Actuarial 5-year survival was 93% for those with TCs and 73% for those with ACs. The mean overall survival was 68 months for the non-metastatic patients (78 months for TC patients and 58 months for AC patients) and 36 months for patients with advanced disease (42 and 32 months, respectively). Conclusion: Cell type is the strongest determinant of prognosis, and the degree of malignancy increases from TCs to ACs. Moreover, the prognosis of metastatic pulmonary carcinoids is not as good as expected. Our analysis suggests that patients with advanced disease should receive first-line therapy with a somatostatin analogue, with chemotherapy regimens (FDE, XELOX) used in progressing cases.

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Prognostic factors in neuroendocrine lung tumors: a Spanish multicenter study

Cited by 141 publications

References 16 publications

Anti-HuC and -HuD autoantibodies are differential sero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung

Anti-HuC and -HuD autoantibodies are differential sero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung

Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas

Pulmonary Carcinoid Tumours: Indolent but Not Benign

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