Potential key roles of tumour budding: a representative malignant pathological feature of non-small cell lung cancer and a sensitive indicator of prognosis

Abstract

ObjectivesTo investigate the relationship between tumour budding, clinicopathological characteristics of patients and prognosis in non-small cell lung cancer.Study designA retrospective study was used.ParticipantsWe selected 532 patients with non-small cell lung cancer from China, including 380 patients with adenocarcinoma and 152 with squamous cell carcinoma.Primary and secondary outcome measuresTumour budding was visible using H&E staining as well as pancytokeratin staining. The count data and measurement data were compared using the χ2 test and the t-test, respectively. The overall survival rate was the follow-up result. The survival curves were drawn using the Kaplan-Meier method, and the differences between groups were analysed using the log-rank method. The independent prognostic factor of patients with lung cancer was determined using a multivariate Cox proportional hazard model.ResultsIn patients with lung adenocarcinoma, there was a correlation between tumour budding and spread through air spaces (OR 36.698; 95% CI 13.925 to 96.715; p<0.001), and in patients with squamous cell carcinoma, tumour budding state was closely related to the peritumoural space (OR 11.667; 95% CI 4.041 to 33.683; p<0.001). On Cox regression analysis, multivariate analysis showed that tumour budding, pleural and vascular invasion, spread through air spaces, tumour size, lymph node metastasis, and tumour node metastasis stage were independent risk factors of prognosis for patients with non-small cell lung cancer.ConclusionsAs an effective and simple pathological diagnostic index, it is necessary to establish an effective grading system in the clinical diagnosis of lung cancer to verify the value of tumour budding as a prognostic indicator. We hope that this analysis of Chinese patients with non-small cell lung cancer can provide useful reference material for the continued study of tumour budding.

Prognostic impact of tumour budding in squamous cell carcinoma of the lung: a systematic review and meta‐analysis

“…Nine studies met our inclusion criteria. [22][23][24][25][26][27][28][29][30] Hand-searching references in eligible studies did not yield new articles.…”

“…All studies were retrospective and conducted in Asia (n = 5), Europe (n = 3) and North America (n = 1). Included studies incorporated the AJCC TNM staging system from the 6th 26 to the 8th editions, 25,29,30 with the 7th edition [22][23][24]27,28 utilised in most studies. Clinical stage I cancer was predominantly observed.…”

“…Five studies reported advanced pathological stages (IIIB-IV) that comprised between 1 and 7% of the individual study population. 22,23,25,27,29 St€ ogbauer et al included two cohorts, The Cancer Genome Atlas (TCGA) and the validation cohort. 30 The TCGA cohort comprised patients with advanced stages, and was therefore not eligible for this review.…”

“…All studies assessed tumour budding on resected tumour specimens; however, whether these specimens were from primary tumour tissue is not clear. Of nine studies, five specifically used primary resected cases 23,25,26,29,30 ; one reported that no neoadjuvant treatment was administered, 27 whereas the remaining studies did not provide this information. Adjuvant therapy was received in 17.1% (16-21%) of the pooled study population.…”

“…All included studies defined tumour budding as an isolated cancer cell or cluster of fewer than five cells. H&E staining was utilised in all included studies; however, three studies included pan-cytokeratin (CK) stains along with H&E 25,26,29 (Figure 2). Taira et al used IHC in tumour budding assessment, whereas Qian et al compared the clarity of the two stains and reported superior clarity with CK staining; however, no statistical tests were used for this comparison.…”