Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung

Garcı́a-Yuste, Mariano; Matilla, José-María; Cueto, Antonio Serrano; Paniagua, J.M. Rodríguez; Ramos, Guillermo; Cañizares, M.A.; Muguruza, Ignacio

doi:10.1016/j.ejcts.2006.11.031

Cited by 186 publications

(153 citation statements)

References 12 publications

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“…2, 4, 5, 11, 27 -29). It is worth noting here that the largest reported series refers mainly to cases collected at different centers, which carries the risk of a different presurgical evaluation, inconsistent surgical management, different handling of the gross specimen for the pathologic assessment, and different adjuvant therapies (1,27,28,30). All such inconsistencies may help to explain the reported variability in patient outcome, particularly for the IG-AC variant.…”

Section: Discussionmentioning

confidence: 95%

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Bronchopulmonary Carcinoid: Phenotype and Long-term Outcome in a Single-Institution Series of Italian Patients

Fassan¹,

Clemente²,

Rizzardi³

et al. 2008

Clinical Cancer Research

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Purpose: The histologic distinction between low-grade typical and intermediate-grade atypical bronchopulmonary carcinoids basically lies on cellular differentiation, mitotic activity, and presence of ''neoplastic'' necrosis; at single patient level, however, none of these features enables a reliable prediction of the clinicopathologic outcome. Experimental Design: The long-term postsurgical outcome of a single-institution series of 67 radically treated bronchopulmonary carcinoids was correlated with the tumor phenotype assessed by combining conventional histology with a panel of immunohistochemical markers exploring cell differentiation (chromogranin, NSE, TTF1), cell turnover (Mib1), and apoptosis (Bcl2, Bax). Results: Fifty-eight (86.6%) carcinoids were assessed as low-grade typical and nine (13.4%) were assessed as intermediate-grade atypical. The mean follow-up was of 85.13 months (range, 28-168; median, 82.0). All cases expressed neuroendocrine markers, whereas TTF1 was never expressed. At univariate analysis, tumor recurrence (n = 6) correlated significantly with the carcinoid histotype (P = 0.002) and with each of the following variables: tumor location (P = 0.01), mitotic index (P = 0.003), necrosis (P = 0.002), tumor vascular invasion (P = 0.0001), Mib1 expression (P = 0.005), Bcl2 expression (P = 0.024), and synchronous node metastasis (P = 0.028).The best cutoffs for Mib1and Bcl2 expression (calculated by receiver operating characteristic curves) discriminating recurrent versus nonrecurrent tumors were 5.4% for Mib1 and 2.0% for Bcl2 (Mib1: sensitivity, 83%; specificity, 97%; area under curve, 0.844 F 0.14; Bcl2: sensitivity, 83%; specificity, 65%; area under curve, 0.769 F 0.12). By stratifying the patients according to the obtained cutoffs, significant differences emerged in the patients' disease-free survival (log-rank test: Mib1, P = 0.0001; Bcl2, P = 0.01). Conclusions: Mib1 and Bcl2 significantly discriminate between recurrent versus nonrecurrent tumors, producing a biologically plausible, diagnostically suitable immunohistochemical pattern.

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Section: Discussionmentioning

confidence: 95%

“…LG-TC is associated with 5-and 10-year survival rates of 87% to 100% and 82% to 92% (26,27), respectively, whereas the atypical variant coincides with a consistently worse, but more variable, outcome (the 5-and 10-year survival rates being 56-78% and 35-67%, respectively; refs. 2, 4, 5, 11, 27 -29).…”

Section: Discussionmentioning

confidence: 99%

Bronchopulmonary Carcinoid: Phenotype and Long-term Outcome in a Single-Institution Series of Italian Patients

Fassan¹,

Clemente²,

Rizzardi³

et al. 2008

Clinical Cancer Research

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“…In the group of atypical carcinoids, CD44 showed a trend toward significance, next to stage. Although histopathology alone is a strong prognostic indicator in the underlying study, classification of lung carcinoids using the WHO criteria may be difficult and its ability to predict the outcome of especially atypical carcinoids varied in previous studies (7)(8)(9). Furthermore, counting mitoses is time consuming and may be difficult, because for example pyknotic apoptotic nuclei and mitoses are hard to distinguish (37,38).…”

Section: Discussionmentioning

confidence: 99%

CD44 and OTP Are Strong Prognostic Markers for Pulmonary Carcinoids

Swarts

Henfling

Neste

et al. 2013

Clinical Cancer Research

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Purpose: Pulmonary carcinoids are well-differentiated neuroendocrine tumors showing usually a favorable prognosis. However, there is a risk for late recurrence and/or distant metastasis. Because histologic classification in typical and atypical carcinoids is difficult and its reliability to predict disease outcome varies, we evaluated three genes as potential prognostic markers, that is, orthopedia homeobox (OTP), CD44, and rearranged during transfection (RET).Experimental Design: These genes were analyzed in 56 frozen carcinoids by quantitative real-time PCR (qRT-PCR). RET was further studied by methylation and mutation analysis. Immunohistochemistry for CD44 and OTP protein expression was conducted on 292 carcinoids.Results: Low mRNA expression levels of CD44 (P ¼ 1.8e À5) and OTP (P ¼ 0.00054), and high levels of RET (P ¼ 0.025), were strongly associated with a low 20-year survival of carcinoid patients. High RET expression was not related to promoter hypomethylation or gene mutations. A direct link between gene expression and protein levels was confirmed for CD44 and OTP but not for RET. Within all carcinoids as well as atypical carcinoids, absence of CD44 protein was significantly associated with low 20-year survival (P ¼ 0.00014 and 0.00013, respectively). The absence of nuclear OTP followed by complete loss of expression was also significantly associated with unfavorable disease outcome in all carcinoids (P ¼ 5. 2 À6 ). Multivariate analyses revealed that age at diagnosis, histopathology, stage, and cytoplasmic OTP immunoreactivity were independent predictors of prognosis.Conclusions: Our study indicates that CD44 and OTP are strong indicators of poor outcome. We therefore argue for implementation of these markers in routine diagnostics in addition to histopathology to improve subclassification of pulmonary carcinoids into prognostically relevant categories.

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“…14) In another studies histological type, pathological stage and lymph node involvement affected the prognosis. 8,15) In our study, histology, lymph node involvement and early distant metastasis appeared as the most important factors affecting the prognosis.…”

Section: Discussionmentioning

confidence: 99%