Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role

Warth, Arne; Cortis, Judith; Soltermann, Alex; Meister, Michael; Budczies, Jan; Stenzinger, Albrecht; Goeppert, Benjamin; Thomas, Michael; Herth, Felix; Schirmacher, Peter; Schnabel, Philipp A.; Hoffmann, Hans; Dienemann, Hendrik; Muley, Thomas; Weichert, Wilko

doi:10.1038/bjc.2014.402

Cited by 113 publications

(111 citation statements)

References 37 publications

(45 reference statements)

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“…1A). These observations are consistent with several previous reports (28)(29)(30). With regard to cPARP staining, the majority of samples showed less than 20% of staining, indicating low levels of intrinsic cell death ( Fig.…”

Section: Resultssupporting

confidence: 93%

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

et al. 2017

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To improve treatment outcomes in non-small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that approximately 70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours. Variations in cisplatin sensitivity were noted with approximately 50% of cases responding ex vivo. Notably, explant responses to cisplatin correlated significantly with patient survival (P ¼ 0.006) irrespective of tumor stage. In explant tissue, cisplatin-resistant tumors excluded platinum ions from tumor areas in contrast to cisplatin-sensitive tumors. Intact TP53 did not predict cisplatin sensitivity, but a positive correlation was observed between cisplatin sensitivity and TP53 mutation status (P ¼ 0.003). Treatment of NSCLC explants with the targeted agent TRAIL revealed differential sensitivity with the majority of tumors resistant to single-agent or cisplatin combination therapy. Overall, our results validated a rapid, reproducible, and low-cost platform for assessing drug responses in patient tumors ex vivo, thereby enabling preclinical testing of novel drugs and helping stratify patients using biomarker evaluation.

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Section: Resultssupporting

confidence: 93%

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

et al. 2017

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“…However, the informative value of the vast majority of studies on this issue is limited by the small sample numbers investigated, different Ki-67 clones used in different studies, and the use of various Ki-67 cutoff points for defining a tumor positive or negative (25). Moreover, subgroup analyses of different NSCLC histologies demonstrate that the prognostic impact of Ki-67 PI depends on the NSCLC type (26) and studies of NSCLC cohorts with mixed histologies will not lead to meaningful results. Despite the large number of published analyses exploring the prognostic role in NSCLC, Ki-67 is still not considered an established factor for routine use in clinical practice.…”

Section: Ki-67 As a Proliferative Markermentioning

confidence: 99%

“…Despite the large number of published analyses exploring the prognostic role in NSCLC, Ki-67 is still not considered an established factor for routine use in clinical practice. A recent study investigated the Ki-67 PI in three large, independent NSCLC cohorts and found the need for use of different cutoff values for each histologic NSCLC type (26). Ki-67 PI was a highly significant and independent predictor for DFS for lung adenocarcinoma and adenosquamous carcinoma, in both the test and validation cohorts, but not for OS and disease-specific survival (DSS) (26).…”

Section: Ki-67 As a Proliferative Markermentioning

confidence: 99%

“…A recent study investigated the Ki-67 PI in three large, independent NSCLC cohorts and found the need for use of different cutoff values for each histologic NSCLC type (26). Ki-67 PI was a highly significant and independent predictor for DFS for lung adenocarcinoma and adenosquamous carcinoma, in both the test and validation cohorts, but not for OS and disease-specific survival (DSS) (26). Interestingly, the authors found that in squamous cell carcinoma a high PI was reversely correlated with a better OS (cut-off value of 50%; HR =0.65; P=0.007).…”

Section: Ki-67 As a Proliferative Markermentioning

confidence: 99%

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Ki-67 expression in pulmonary tumors

Chirieac

2016

Transl. Lung Cancer Res.

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“…[13][14][15][16][17][18][19] The Ki-67 index has also been used routinely in the evaluation of lung tumours and has been shown to be an important prognostic factor for lung cancer. 3,6,[20][21][22][23][24][25][26][27] Although a few studies have evaluated the association of ADC with Ki-67 index in lung tumours 3,6 , no study has previously investigated differences in the ADC/Ki 67 correlation in different tumour subtypes.…”

Section: Introductionmentioning

confidence: 99%

Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer

et al. 2016

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Disclosure: No potential conflicts of interest were disclosed.Background. The primary objective of the study was to evaluate the association between the minimum apparent diffusion coefficient (ADC min ) and Ki-67, an index for cellular proliferation, in non-small cell lung cancers. Also, we aimed to assess whether ADC min values differ between tumour subtypes and tissue sampling method.Methods. The patients who had diffusion weighted magnetic resonance imaging (DW-MRI) were enrolled retrospectively. The correlation between ADC min and the Ki-67 index was evaluated.Results. Ninety three patients, with a mean age 65 ± 11 years, with histopathologically proven adenocarcinoma and squamous cell carcinoma of the lungs and had technically successful DW-MRI were included in the study. The numbers of tumour subtypes were 47 for adenocarcinoma and 46 for squamous cell carcinoma. There was a good negative correlation between ADC min values and the Ki-67 proliferation index (r = -0.837, p < 0.001). The mean ADC min value was higher and the mean Ki-67 index was lower in adenocarcinomas compared to squamous cell carcinoma (p < 0.0001). There was no statistical difference between tissue sampling methods.Conclusions. Because ADC min shows a good but negative correlation with Ki-67 index, it provides an opportunity to evaluate tumours and their aggressiveness and may be helpful in the differentiation of subtypes non-invasively.

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Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role

Cited by 113 publications

References 37 publications

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy

Ki-67 expression in pulmonary tumors

Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer

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