Tumor budding is a significant indicator of a poor prognosis in lung squamous cell carcinoma patients

Abstract

Lung cancer is a leading cause of cancer mortality worldwide and patients occasionally develop local recurrence or distant metastasis soon after curative resection. Reports of new therapeutic strategies for lung squamous cell carcinoma (SqCC) are extremely rare, while selective anticancer therapy has been reported for lung adenocarcinoma. The aim of this study was to identify clinicopathological prognostic factors for SqCC. We analyzed tumor budding and infiltrative patterns (INF) in 103 cases of surgically-resected SqCC. Tumor infiltrative patterns were classified into three groups (INFa, b and c) and INFc was infiltrative growth at the tumor invasive front. The cases with an INFc component [INFc(+)]were significantly associated with venous invasion (P=0.014) and the scirrhous stromal type (P<0.001). The overall survival rate of patients with INFc(+) was significantly lower than that of patients without the INFc component [INFc(−); P=0.003]. Tumor budding was defined as a single cancer cell or a small nest of up to four cancer cells within stromal tissue. The cases with tumor budding [Bud(+)] were significantly associated with lymph node metastasis (P=0.001), lymphatic invasion (P=0.002), INFc(+) (P<0.001) and the scirrhous stromal type (P=0.014). Patients with the Bud(+) type had a lower overall survival rate than patients with the Bud(−) type (P<0.001). Multivariate analysis demonstrated that tumor budding [hazard ratio (HR), 2.766; 95% confidence interval (CI), 1.497–5.109] and lymph node metastasis (HR, 1.937; 95% CI, 1.097–3.419) were independent predictors of mortality. In conclusion, tumor budding is a significant indicator of a high malignant potential and poor prognosis in SqCC of the lung.

Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a Histological Marker of Increased Tumor Invasiveness

“…Alternative histologic parameters such as tumor budding have been proposed as various measures of tumor invasion in cancers notably in colorectal carcinoma (36)(37)(38). In NSCLC, single cells, tumor buds (<5 cells) or nests ( 15 cells) together with stroma thickness have also shown an impact on patient's survival (2,3,39,40), although small invasive tumor clusters are less frequent in LSCC. As shown in Fig.…”

Spread through air spaces (STAS): a comprehensive update

“…The prognostic impact of STAS in SCC was most recently confirmed in a series of 2016 cases from Japan (17). Thus, beyond budding and cell nest size which has previously been identified as prognostically relevant morphological parameters in SCC (18)(19)(20)(21), STAS seems to be another morphological feature to allow for a better prognostic stratification of SCC and potentially the establishment of a clinically meaningful grading system in the near future.…”

Laminin-5^|^gamma;2 chain expression is associated with tumor cell invasiveness and prognosis of lung squamous cell carcinoma

“…In our previous study, we classified INF patterns of lung squamous cell carcinomas (SqCC) into two groups, i.e., cases with an INFc component (INFc(+)) and those without an INFc component (INFc(−)), and INFc(+) showed a poorer outcome compared to INFc(−) (19). Furthermore, tumor budding was a poorly-differentiated component at the invasive front (8), and shows locally aggressive growth.…”