Basal Ki67 expression measured by digital image analysis is optimal for prognostication in oral squamous cell carcinoma

Background. Oral cancer is revisited on a pathologist perspective with advanced imaging technique.Objective. The present study assessed the new malignancy grading system at tumor proper (TP) and Bryne’s grading system at invasive tumor front (ITF), morphometric features using software, to clarify their associations with prognosis of oral cancers.Methods. Histologically confirmed oral squamous cell carcinoma (OSCC) with 5-year follow-up was assessed morphometrically using image analysis at TP and ITF, correlated with the prognosis of patient.Results. On comparison of grading systems, a moderate agreement between both (Bryne and Anneroth) was seen. Among all histological parameters, we noted inverse correlation between degree of mitosis at invasive front and decrease in lymphoplasmacytic infiltrate at ITF with increase rate of recurrence and event of death. An increase in nuclear area, diameter, and perimeter along with decrease circularity in advancing OSCC was seen. Correlation of parameters showed higher values for maximum nuclear diameter, perimeter, and circularity at TP and ITF with recurrence.Conclusion. This study, while limited in sample size, concluded that a combined assessment of clinical TNM staging, histopathological grading system{excluding the parameter “mitotic activity” (due to its inverse relation)}, and nuclear morphometry at the ITF are better prognosticators. This combination proved to be an accurate predictive factor in eliciting the varied molecular characteristics of tumor heterogeneity.

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Higher Ki67 expression in fibroblast like cells at invasive front indicates better clinical outcomes in oral squamous cell carcinoma patients

Bioscience Reports ◽

10.1042/bsr20181271 ◽

2018 ◽

Vol 38 (6) ◽

Author(s):

Yue Jing ◽

Yan Yang ◽

Fengyao Hao ◽

Yuxian Song ◽

Xiaoxin Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Multivariate Analysis ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Clinical Outcomes ◽

Squamous Cell ◽

Clinicopathological Parameters ◽

Invasive Front ◽

Ki67 Expression ◽

Spatial Expression

Background: Ki67 has been a key role for the treatment options and prognosis evaluation in some kinds of tumors; however, the spatial expression of Ki67 in oral squamous cell carcinoma (OSCC) has not been fully-evaluated. Therefore, in the present study, we aimed to elucidate the prognosis value of Ki67 spatial expression including in different cell types and at different compartments of tumor in OSCC patients. Methods: Immunohistochemical expression of Ki67 in tumor cells (TCs) and fibroblast like cells (FLCs) at center of tumor (CT) and invasive front (IF) was evaluated in 109 OSCC patients. Then correlations of Ki67 expressions with clinicopathological parameters were analyzed by Chi-square test, and survival curves were evaluated by Kaplan–Meier methods. Furthermore, univariate and multivariate analysis were performed to assess the diagnostic values of Ki67 expression by the Cox regression model. Results: Ki67 expression in TCs was much higher than in FLCs both at CT and IF compartments, but Ki67 expression in TCs was simultaneously higher at CT than that at IF (P=0.0004), which was converse to Ki67 expression in FLCs (P<0.0001). Additionally, high Ki67 expression in FLCs at IF was significantly associated with poor tumor differentiation (P=0.003), worse depth of invasion (DOI, P=0.027) and worst pattern of invasion (WPOI, P=0.041), but Ki67 expression in TCs had no correlation with clinical parameters no matter at CT or IF. Moreover, patients with higher Ki67 expression in TCs at CT had significantly increased risk for OS (overall survival; HR:1.935, 95% CI: 1.181–4.823, P=0.0395) and DFS (disease-free survival; HR: 2.974, 95% CI:1.189–5.023, P=0.046). On contrary, higher Ki67 expression in FLCs at IF was correlated with better OS (HR: 0.15, 95% CI: 0.018–0.846, P=0.0396) and DFS (HR: 0.15, 95% CI: 0.018–0.947, P=0.0445). Whereas, Ki67 expression both at TCs in IF and at FLCs in CT had no significant prognostic value for OS and DFS. Furthermore, Cox multivariate analysis revealed that Ki67 expression in FLCs at IF could not be an independent prognostic factor for OSCC patients. Conclusion: These results show that higher Ki67 expression in FLCs at IF indicated better clinical outcomes for OSCC patients.

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