Analysis of <scp>NSCLC</scp> tumour heterogeneity, proliferative and 18F‐<scp>FDG PET</scp> indices reveals Ki67 prognostic role in adenocarcinomas

Gobbo, Alessandro Del; Pellegrinelli, Alessio; Gaudioso, Gabriella; Castellani, Massimo; Marino, Federica Zito; Franco, Renato; Palleschi, Alessandro; Nosotti, Mario; Bòsari, Silvano; Vaira, Valentina; Ferrero, Stefano

doi:10.1111/his.12808

Cited by 43 publications

(38 citation statements)

References 15 publications

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“…In addition, Ki67 is also used as a prognostic and diagnostic index for the evaluation of cancer biopsies, including lung cancer [11, 12]. Our results confirmed that Ki67 was an independent prognostic factor in NSCLC (Table 2).…”

Section: Discussionsupporting

confidence: 80%

Elevated fibrous sheath interacting protein 1 levels are associated with poor prognosis in non-small cell lung cancer patients

Mao

et al. 2017

Oncotarget

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In this study, we examined the expression and prognostic value of fibrous sheath interacting protein 1 (FSIP1) in 202 non-small cell lung cancer (NSCLC) patients who underwent lung cancer resection at Shengjing Hospital of China Medical University. FSIP1 mRNA and protein expression were measured in NSCLC tissues and non-tumor adjacent tissues (NATs), and Harrell's concordance index (c-index) was used to evaluate the ability of FSIP1 to predict prognosis. FSIP1 mRNA and protein expression was higher in NSCLC tissues than in NATs. Survival analysis revealed the 5-year overall survival rate to be 35.4% in the FSIP1-positive group and 56.3% in the FSIP1-negative group, and FSIP1-positive status was an independent prognostic factor for poor overall survival. The c-index value of FSIP1 for overall survival was greater than that of Ki67, and the addition of FSIP1 status increased the c-index value of the TNM staging system. These results suggest that evaluating FSIP1 status in addition to TNM stage during routine pathological examinations could improve prognostic predictions in NSCLC patients.

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Section: Discussionsupporting

confidence: 80%

Elevated fibrous sheath interacting protein 1 levels are associated with poor prognosis in non-small cell lung cancer patients

Mao

et al. 2017

Oncotarget

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“…Prior studies of human NSCLC have identified intratumoral heterogeneity in terms of proliferative activity [30], cellular histology [31], anaplastic lymphoma kinase rearrangements [32], and PD-L1 expression [9]. Thus, heterogeneity of CD8 + T cell infiltrations is expected.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of CD8+ tumor-infiltrating lymphocytes in non-small-cell lung cancer: impact on patient prognostic assessments and comparison of quantification by different sampling strategies

Obeid

Wages

et al. 2016

Cancer Immunol Immunother

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Introduction Infiltration of non-small-cell lung cancer (NSCLC) by CD8+ T lymphocytes predicts improved patient survival; however, heterogeneity of intratumoral localization complicates this assessment. Strategies for tumor sampling may not accurately represent the whole tumor. We hypothesized that sampling strategies may alter the identification of tumors with high CD8 density and affect the prognostic significance. Patients and methods Twenty-three primary NSCLC tumors were immunohistochemically stained for CD8 and were assessed using automated software with eight different sampling strategies or the whole tumor. Results of all sampling strategies were compared to the whole tumor counts (paired t tests, Pearson’s r). Associations between CD8 densities and overall survival were assessed (log-rank test). Results Counts from all eight sampling strategies significantly correlated with whole tumor counts (p ≤ 0.001). However, the magnitude of CD8+ cell counts and categorization into high vs low infiltrate groups were affected by the sampling strategy. The most concordant values were derived from random sampling of 20 % of the tumor, a simulated core biopsy, or from sampling the tumor center. TIL infiltration was associated with survival when sampling the center (p = 0.038), but not the invasive margin (p > 0.2) or other strategies. Conclusion Different tumor sampling strategies may yield discordant TIL density results and different stratification for risk assessment. Small biopsies may be particularly unrepresentative. Random sampling of larger tumor areas is recommended. Enumerating CD8+ T cells in the tumor center may have prognostic value.

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“…It is present in all active phases of the cell cycle, but absent from resting cells, thus, indicating the proliferating cell fraction (39). Ki-67 is a prognostic biomarker in several tumor entities, for example, breast cancer, lymphoma, neuroendocrine neoplasia and NSCLC (40)(41)(42)(43)(44)(45). The Ki-67 index could also be employed to investigate the association between Testin expression and NSCLC cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Testin is a tumor suppressor in non-small cell lung cancer

Wang

Peng

et al. 2016

Oncology Reports

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Abstract. The Testin gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. It has been implicated in several types of cancers including prostate, ovarian, breast and gastric cancer. In the present study, we investigated the function of the candidate tumor-suppressor Testin gene in non-small cell lung cancer (NSCLC). In NSCLC cell lines, we observed lower expression of Testin compared to that noted in normal human bronchial epithelial cells. MTT assays, flow cytometry, clonogenic assay and invasion assay showed that the overexpression of the Testin gene inhibited cancer cell proliferation, invasion and colony formation. In tumor xenograft models, Testin markedly inhibited lung cancer cell xenograft formation and growth in athymic nude mice. Taken together, these data suggest that Testin plays an important role in the development and progression of NSCLC. Testin may be an effective novel target in NSCLC prevention and treatment.

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Analysis of NSCLC tumour heterogeneity, proliferative and 18F‐FDG PET indices reveals Ki67 prognostic role in adenocarcinomas

Cited by 43 publications

References 15 publications

Elevated fibrous sheath interacting protein 1 levels are associated with poor prognosis in non-small cell lung cancer patients

Elevated fibrous sheath interacting protein 1 levels are associated with poor prognosis in non-small cell lung cancer patients

Heterogeneity of CD8+ tumor-infiltrating lymphocytes in non-small-cell lung cancer: impact on patient prognostic assessments and comparison of quantification by different sampling strategies

Testin is a tumor suppressor in non-small cell lung cancer

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