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. 2012 Nov;6(5):937-43.
doi: 10.3892/mmr.2012.1048. Epub 2012 Aug 27.

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

Ryota Masuda  1 , Hiroshi Kijima, Naoko Imamura, Naohiro Aruga, Yusuke Nakamura, Daisuke Masuda, Haruka Takeichi, Nobusuke Kato, Tomoki Nakagawa, Makiko Tanaka, Sadaki Inokuchi, Masayuki Iwazaki
Affiliations

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

Ryota Masuda et al. Mol Med Rep. 2012 Nov.

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.

Keywords: lung cancer; squamous cell carcinoma; patient prognosis; tumor budding.

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Figures

Figure 1
Figure 1
Microscopic findings of lung squamous cell carcinoma (hematoxylin and eosin staining). Tumor infiltrative patterns (INF) at the invasive front are classified into three groups: (A) INFa, cancer nests show an expansion in growth and a distinct border with the surrounding tissue; (B) INFb, the manner of growth and invasive pattern are between those of INFa and INFc; and (C) INFc, cancer nests show infiltrative growth and the borderline with the surrounding tissue is unclear.
Figure 2
Figure 2
Microscopic findings of lung squamous cell carcinoma (hematoxylin and eosin staining). Tumor budding is defined as single cancer cells and/or clusters composed of up to four cancer cells. (A) One, (B) two and (C) three budding foci.
Figure 3
Figure 3
Tumor infiltrative patterns and cumulative survival of patients with lung squamous cell carcinoma. INFc(−)/INFc(+), tumor infiltrative pattern group c component-negative/positive.
Figure 4
Figure 4
Tumor budding and cumulative survival of patients with lung squamous cell carcinoma.
See this image and copyright information in PMC

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