Gender difference in the prognostic role of interleukin 6 in oral squamous cell carcinoma

Abstract

Background: Interleukin 6 (IL6) plays an important role in immunoregulation and tumorigenesis in human cancers. Oral squamous cell carcinoma (OSCC) is a malignant tumor of the oral cavity with a male predominant tendency and a poor clinical prognosis. Due to the relatively few cases in females, the gender difference of prognostic markers for OSCC is seldom discussed.

Methods: In this study, we used immunohistochemical staining methods to investigate the associations between IL6 expression and the clinicopathological characteristics of OSCC. In addition, we collected 74 female and 263 male OSCC patients for evaluation.

Results: High IL6 expression in tumor cells was significantly associated OSCC patient characteristics including female gender (P<0.001), high lymph node metastatic rate (P = 0.007), and poor tumor differentiation (P = 0.008). Tumor-expressed IL6 had prognostic role in male OSCC patients as defined by the log-rank test (P = 0.014), but not in female patients (P = 0.959). In male OSCC patients, high IL6 expression in tumor cells was associated with poor prognosis (P = 0.025) and a 1.454-fold higher death risk, as determined by Cox regression.

Conclusions: High IL6 expression in tumor cells was therefore significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in male OSCC patients.

Figure 1. Representative immunohistochemical (IHC) staining patterns of tumor tissues for IL6 immunoreactivity in oral squamous cell carcinoma (OSCC).

(A) Negative or barely conspicuous cytoplasmic staining (intensity = 0). (B) Weak cytoplasmic staining in OSCC (intensity = 1+). (C) Moderate cytoplasmic staining in OSCC (intensity = 2+). (D) Strong cytoplasmic staining in OSCC (intensity = 3+). (Immunohistochemistry: original magnification×200).

Figure 2. Representative IHC staining patterns for IL6 in normal oral epithelium (A) showing negative or barely conspicuous cytoplasmic staining (intensity = 0), hyperplastic oral epithelium (B) showing negative or barely conspicuous cytoplasmic staining (intensity = 0) and dysplastic oral epithelium (C) showing weak cytoplasmic staining (intensity = 1+).

(Immunohistochemistry: original magnification×200).

Figure 3. Analysis of the overall survival of patients with varying immunoreactivities of tumor tissues for IL6 expression.

(A) Kaplan-Meier survival curves for OSCC patients who were classified with either low/negative (weak (1+) or negative (−) IHC positivity) or high IL6 (strong (3+) or moderate (2+) IHC positivity) expression. The IL6 status was not significantly associated (log-rank, P = 0.134) with patient survival. (B) In male OSCC patients, the IL6 status was significantly associated (log-rank, P = 0.014) with patient survival. (C) In female OSCC patients, no significant association was found for IL6 expression and patient survival (log-rank, P = 0.959).