The clinicopathologic significance of the expression of HLA-G in oral squamous cell carcinoma.

This study aimed to evaluate HLA-G expression in primary oral cavity squamous cell carcinoma (OCSCC) and potentially malignant lesions and to evaluate its relationship with clinicopathologic parameters. HLA-G expression in samples from patients with metastatic and nonmetastatic OCSCC (n = 60), potentially malignant lesions (n = 15), and clinically and histologically normal oral mucosa (n = 10) was characterized by immunohistochemistry. The density of CD8, CD83, and CD68 cells and Ki-67(+) and bcl-2(+) neoplastic cells were analyzed. HLA-G expression by neoplastic cells was significantly higher in metastatic OCSCC compared with nonmetastatic OCSCC (P = .01). Higher HLA-G expression was observed in OCSCC than in potentially malignant lesions (P = .006). Moreover, patients with lower HLA-G expression exhibited a tendency toward longer survival (22 months) compared with those with higher HLA-G expression (16 months). Our findings suggest that increased HLA-G expression in metastatic OCSCC may represent a tumor escape mechanism, which portends an unfavorable clinical prognosis.

Gonçalves AS ，Wastowski IJ ，Capeletti LR ，Sacono NT ，Cortez AP ，Valadares MC ，Silva TA ，Batista AC ... -  《-》

Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma.

To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p<0.05. The data showed a predominance of M2 phenotype (high percentage of IL-10(+)TGF-β(+)) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time.

Costa NL ，Valadares MC ，Souza PP ，Mendonça EF ，Oliveira JC ，Silva TA ，Batista AC ... -  《-》

Differential infiltration of CD8+ and NK cells in lip and oral cavity squamous cell carcinoma.

Zancope E ，Costa NL ，Junqueira-Kipnis AP ，Valadares MC ，Silva TA ，Leles CR ，Mendonça EF ，Batista AC ... -  《-》

Midkine expression in oral squamous cell carcinoma and leukoplakia.

Midkine (MK), a 13-kDa heparin-binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control). Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki-67, PCNA, p53, bcl-2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK(+) cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated. The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late-stage tumors (T3/T4) compared with early-stage lesions (T1/T2). MK-positive lesions also showed increased expression of the anti-apoptotic protein bcl-2. OCSCC, particularly late-stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti-apoptotic genes, as shown by the augmented bcl-2 positivity in MK-positive tumors.

Jham BC ，Costa NL ，Silva JM ，de Miranda AC ，Oliveira JC ，Silva TA ，Batista AC ... -  《-》

The clinicopathological significance of the expression of Granzyme B in oral squamous cell carcinoma.

Granzyme B (GB) is a serine protease synthesized by activated cytotoxic T-lymphocytes and natural killer cells that induces neoplastic cells apoptosis. The expression of GB in the tumor microenvironment has been considered a favorable prognostic factor in several types of human cancers. Thus, the aim of this study was to evaluate the density of GB(+) cells in samples of oral cavity squamous cell carcinoma (OCSCC), as well as their relationship with clinical and microscopic parameters. GB expression was analyzed in 55 cases of OCSCC and metastatic and non-metastatic lymph nodes by means of immunohistochemistry. The high density of GB(+) cells demonstrated an association with the high percentage of Bax(+) and annexin V(+) neoplastic cells. In addition, the number of peritumoral GB(+) cells was significantly higher in the OCSCC group without lymph node metastasis, when compared with the metastatic OCSCC group. Moreover, patients with OCSCC with a high density of peritumoral GB(+) cells showed a longer survival time when compared with patients with a lower density of these cells. In lymph node tissues, the density of GB(+) cells was significantly higher in non-metastatic lymph nodes than in metastatic lymph nodes. Our findings suggest that the increased of expression of GB in the tumor microenvironment of OCSCC and in lymph nodes may have beneficial effect against neoplastic cells, contributing to apoptosis of these cells and increased survival of patients.

Costa NL ，Alencar Rde C ，Valadares MC ，Silva TA ，Mendonça EF ，Batista AC ... -  《-》