Correlation of neuroendocrine features with prognosis of non-small cell lung cancer

Feng, Jianguo; Sheng, Huaying; Zhu, Chihong; Qian, Xiaoqian; Danying, Wan; Su, Dan; Zhu, Liming

doi:10.18632/oncotarget.12327

Cited by 30 publications

(21 citation statements)

References 37 publications

(22 reference statements)

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“…Thus, the information derived from both diagnostic tools could enhance our understanding of this aggressive and insufficiently investigated tumor entity. In our analysis, the lack of synaptophysin expression correlated with a worse OS, contrary to what is reported for NSCLCs (45,46), whereas lack of chromogranin A correlated with the presence of cerebral metastases at diagnosis. Both neuroendocrine markers play a significant role in the diagnosis, but little is known about the prognosis of SCLC who lack expression of neuroendocrine markers.…”

Section: Discussioncontrasting

confidence: 99%

Immunohistochemistry and Radiomic Features for Survival Prediction in Small Cell Lung Cancer

et al. 2020

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Background: The aim of the study was to evaluate the role of different immunohistochemical and radiomics features in patients with small cell lung cancer (SCLC). Methods: Consecutive patients with histologically proven SCLC with limited (n = 47, 48%) or extensive disease (n = 51, 52%) treated with radiotherapy and chemotherapy at our department were included in the analysis. The expression of different immunohistochemical markers from the initial tissue biopsy, such as CD56, CD44, chromogranin A, synaptophysin, TTF-1, GLUT-1, Hif-1 a, PD-1, and PD-L1, and MIB-1/KI-67 as well as LDH und NSE from the initial blood sample were evaluated. H-scores were additionally generated for CD44, Hif-1a, and GLUT-1. A total of 72 computer tomography (CT) radiomics texture features from a homogenous subgroup (n = 31) of patients were correlated with the immunohistochemistry, the survival (OS), and the progression-free survival (PFS). Results: The median OS, calculated from diagnosis, was 21 months for patients with limited disease and 13 months for patients with extensive disease. The expression of synaptophysin correlated with a better OS (HR 0.546 95% CI 0.308-0.966, p = 0.03). The expression of TTF-1 (HR 0.286, 95% CI: 0.117-0.698, p = 0.006) and a lower GLUT-1 H-score (median = 50, HR: 0.511, 95% CI: 0.260-1.003, p = 0.05) correlated with a better PFS. Patients without chromogranin A expression had a higher risk for developing cerebral metastases (p = 0.02) and patients with PD 1 expression were at risk for developing metastases (p = 0.02). Our radiomics analysis did not reveal a single texture feature that correlated highly with OS or PFS. Correlation coefficients ranged between −0.48 and 0.39 for OS and between −0.46 and 0.38 for PFS. Gkika et al. Immunohistochemistry and Radiomics in SCLC Conclusions: The role of synaptophysin should be further evaluated as synaptophysin-negative patients might profit from treatment intensification. We report an, at most, moderate correlation of radiomics features with overall and progression free survival and no correlation with the expression of different immunohistochemical markers.

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Section: Discussioncontrasting

confidence: 99%

Immunohistochemistry and Radiomic Features for Survival Prediction in Small Cell Lung Cancer

et al. 2020

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“…In our literature search, 8% (149 of 1777) of NSCLCs were positive for at least 2 of CD56, chromogranin A, and synaptophysin (see Supplemental Table 1), but it is noteworthy that the frequency was less than 2% in 3 studies (including our study; see Figure 2, B), 15,27 while it was exceedingly high in 2 studies (19% and 55%), which led to the overall high occurrence. 29,32 The frequency of positive NE markers is reported to be rather high in non-NE components of combined LCNEC or SCLC. 54 Recently, it has been debated whether staining with NE markers should be performed in all poorly differentiated NSCLC cases (in addition to AC and SqCC markers), 55,56 but since there is no consistent evidence of clinical relevance, 29,32,43,47 it is advisable to apply IHC NE markers only when NE morphology is suggested.…”

Section: Discussionmentioning

confidence: 99%

“…29,32 The frequency of positive NE markers is reported to be rather high in non-NE components of combined LCNEC or SCLC. 54 Recently, it has been debated whether staining with NE markers should be performed in all poorly differentiated NSCLC cases (in addition to AC and SqCC markers), 55,56 but since there is no consistent evidence of clinical relevance, 29,32,43,47 it is advisable to apply IHC NE markers only when NE morphology is suggested. 1,16,56 If strictly limiting to obvious NE morphology, it would probably be advantageous to use the most sensitive IHC NE markers (tentatively CD56 in combination with synaptophysin and/ or INSM1).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Staaf

Tran²,

Söderlund³

et al. 2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non–small cell lung carcinomas (NSCLCs) is clinically relevant for prognostication and treatment. Diagnosis is based on morphology and immunohistochemical staining. Objective.— To determine the diagnostic value of insulinoma-associated protein 1 (INSM1), in comparison with established NE markers, in pulmonary tumors. Design.— Fifty-four pulmonary NE tumors and 632 NSCLCs were stained for INSM1, CD56, chromogranin A, and synaptophysin. In a subset, gene expression data were available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 39 additional studies with data on NE markers in lung cancers from the last 15 years. Seven of these included data on INSM1. Results.— A positive INSM1 staining was seen in 39 of 54 NE tumors (72%) and 6 of 623 NSCLCs (1%). The corresponding numbers were 47 of 54 (87%) and 14 of 626 (2%) for CD56, 30 of 54 (56%) and 6 of 629 (1%) for chromogranin A, and 46 of 54 (85%) and 49 of 630 (8%) for synaptophysin, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity, while synaptophysin also showed good sensitivity. INSM1 gene expression was clearly associated with NE histology. Conclusions.— The solid data of both our and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 and/or synaptophysin should be the first-hand choice to confirm pulmonary high-grade NE tumors. INSM1 gene expression could be used to predict NE tumor histology.

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“…Embryonic nuclear determinants of NE differentiation in the lung, such as human achaete-scute homolog 1 (hASH1), are usually lost or poorly expressed in carcinoids but retained by high-grade tumors, especially SCLC (76,77), whereas membrane-based NCAM/CD56 is sensitive but less specific for NE differentiation (1,78). The latter is expressed in all Lu-NETs, especially SCLC (40,(77)(78)(79), but can turn out positive also in conventional NSCC (80), various sarcomas (81,82) and malignant mesothelioma (83). High molecular weight keratins (CK), such as those recognized by the clone 34βE12 (CK1, CK5, CK10 and CK14), are consistently negative in Lu-NETs (84).…”

Section: Diagnosis and Classification Of Pulmonary Neuroendocrine Tumorsmentioning

confidence: 99%

Classification of pulmonary neuroendocrine tumors: new insights

Pelosi¹,

Sonzogni²,

Harari³

et al. 2017

Transl. Lung Cancer Res.

117

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Neuroendocrine tumors of the lung (Lu-NETs) embrace a heterogeneous family of neoplasms classified into four histological variants, namely typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). Defining criteria on resection specimens include mitotic count in 2 mm and the presence or absence of necrosis, alongside a constellation of cytological and histological traits including cell size and shape, nuclear features and overall architecture. Clinically, TC are low-grade malignant tumors, AC intermediate-grade malignant tumors and SCLC/LCNEC high-grade malignant full-blown carcinomas with no significant differences in survival between them. Homologous tumors arise in the thymus that occasionally have some difficulties in differentiating from the lung counterparts when presented with large unresectable or metastatic lesions. Immunohistochemistry (IHC) helps refine NE diagnosis at various anatomical sites, particularly on small-sized tissue material, in which only TC and small cell carcinoma categories can be recognized easily on hematoxylin & eosin stain, while AC and LCNEC can only be suggested on such material. The Ki-67 labeling index effectively separates carcinoids from small cell carcinoma and may prove useful for the clinical management of a metastatic disease to help the therapeutic decision-making process. Although carcinoids and high-grade neuroendocrine carcinomas in the lung and elsewhere make up separate tumor categories on molecular grounds, emerging data supports the concept of secondary high-grade NETs arising in the preexisting carcinoids, whose clinical and biological relevance will have to be placed into the proper context for the optimal management of these patients. In this review, we will discuss the selected, recent literature with a focus on current issues regarding Lu-NET nosology, i.e., classification, derivation and tumor evolution.

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Correlation of neuroendocrine features with prognosis of non-small cell lung cancer

Cited by 30 publications

References 37 publications

Immunohistochemistry and Radiomic Features for Survival Prediction in Small Cell Lung Cancer

Immunohistochemistry and Radiomic Features for Survival Prediction in Small Cell Lung Cancer

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Classification of pulmonary neuroendocrine tumors: new insights

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