Distribution and significance of interstitial fibrosis and stroma-infiltrating B cells in tongue squamous cell carcinoma - PubMed (original) (raw)

Distribution and significance of interstitial fibrosis and stroma-infiltrating B cells in tongue squamous cell carcinoma

Xiao-Mei Lao et al. Oncol Lett. 2016 Mar.

Abstract

Inflammation and desmoplasia are frequently identified in the tumor microenvironment, and have been demonstrated to be effective modulators of malignant biological events. However, the mechanisms by which the inflammatory microenvironment and interstitial fibrosis interact with one another remain to be elucidated. The present study aimed to investigate the degree of inflammation and interstitial fibrosis in tongue squamous cell carcinoma (TSCC), and how this acts to affect the outcome of TSCC. Tissue samples from 93 cases of TSCC and paired tumor-adjacent non-neoplastic tongue epithelium, as well as 14 cases of epithelial dysplasia, were used. Interstitial collagen fibers were assessed using Masson's trichrome stain. Immunohistochemical identification of cancer-associated fibroblasts (CAFs) and stroma-infiltrating B cells was performed via detection of α-smooth muscle actin (SMA), vimentin, desmin and cluster of differentiation 19 (CD19). The clinicopathological significance and overall survival of the TSCC patients were statistically analyzed. Regularly distributed CAFs and CD19+ B cells were identified in the TSCC stroma, whereas no CAFs or CD19+ B cells were observed in epithelial dysplasia samples or paired tumor-adjacent non-neoplastic tongue epithelium samples. The distribution of interstitial collagen fibers and CAFs was closely associated with the tumor stage of the primary cancer, and high levels of CD19+ B cells together with low CAF infiltration were identified to be associated with favorable prognosis in TSCC. In conclusion, the inflammatory and interstitial fibrotic microenvironments coexist in TSCC, and each has specific effects on disease outcome, individually or perhaps collectively. However, it remains to be determined exactly how the microenvironments affect one another in TSCC.

Keywords: cancer-associated fibroblasts; inflammatory microenvironment; interstitial fibrosis; stroma-infiltrating B cells; tongue squamous cell carcinoma.

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Figures

Figure 1.

Figure 1.

Semi-quantification image analysis of stromal collagen fibers. (A) Original Masson's trichrome stained image of the tissue section. Distinction of the cell compartment (red) and collagen fiber (blue) is clear. (B) Area of the stroma from image A demonstrating removal of the epithelial cell compartments. (C) Area of the interstitial collagen fiber compartment; all other areas removed, with the exception of the fibrous area from image B. Magnification, ×200.

Figure 2.

Figure 2.

Distribution patterns of interstitial collagen fibers in the tissue samples. (A) No positive staining of interstitial collagen fibers was observed in the paired tumor-adjacent non-neoplastic tongue epithelium samples. (B) In the epithelial dysplasia samples, profuse interstitial collagen fibers were identified. (C) Dense and well-organized, parallel bundles of collagen fibers surrounding the tumor nest. (D) Complex fibers existed in large quantities around the cancer cells that were in the stroma. Magnification, ×200.

Figure 3.

Figure 3.

Association between average %CFC and the T stage of tongue squamous cell carcinoma. Tumor interstitial CFC indicated a trend for increasing as the tumor increased in size, with the exception of T1 stage cases. The data is presented as the mean ± standard deviation. CFC, collagen fiber content; T, tumor.

Figure 4.

Figure 4.

Immunohistochemical staining of CAFs. CAFs were (A) α-SMA and (B) vimentin positive, but (C) desmin negative. (D and E) Negative staining of α-SMA in the epithelial dysplasia and paired tumor-adjacent non-neoplastic tongue epithelium samples. (F) Typical ‘network’ pattern formed when CAFs are particularly abundant and occupy almost the entire tumor stroma. (G) ‘Spindle’ pattern, in which CAFs are arranged in 1–3 rows in a regular order in the periphery of the neoplastic islands. CAFs, cancer-associated fibroblasts; SMA, smooth muscle actin.

Figure 5.

Figure 5.

Follicular aggregates of stroma-infiltrating B cells in the stroma of tongue squamous cell carcinoma, exhibiting the ‘Crohn's-like reaction’.

Figure 6.

Figure 6.

Kaplan-Meier survival curves for tongue squamous cell carcinoma patients according to (A) α-SMA and (B) CD19 staining in the tumor stroma. The log-rank test revealed that the survival rate between various scores of α-SMA staining was not statistically significant (P=0.504), however, a statistically significant difference was observed between various scores of CD19 expression (P=0.008). SMA, smooth muscle actin; CD, cluster of differentiation.

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