Hormone receptors AR, ER, PR and growth factor receptor Her-2 expression in oral squamous cell carcinoma: Correlation with overall survival, disease-free survival and 10-year survival in a high-risk population

Oral squamous cell carcinoma (OSCC) comprises most of head and neck neoplasms and is one of the highest-ranking and lethal cancers in Pakistan due to prevailing mouth habits. Growth and hormonal receptors act as prognostic markers and targets for therapy in some cancers, but their application in OSCC is largely unexplored. This study aimed to evaluate the expression of growth and hormonal receptors in OSCC patients and correlate it with 10-year, overall and disease-free survival. To achieve this objective, immunohistochemistry for Her-2, AR, ER and PR was performed on 100 formalin-fixed paraffin-embedded primary OSCC specimens. Receptor expression was correlated with mouth habits and clinicopathological features and patient survival was analyzed using Kaplan-Meier method and Cox regression univariate analysis. We observed that in 100 patients, there were 57 males and 43 females. Immunopositive Her-2 expression was observed in 21% of patients, AR in 13%, ER in 3% and 0% for PR. Patients with betel quid/areca nut mouth habits had significantly absent Her-2 expression (P=0.035). Also, Her-2 negative patients were also negative for AR expression (P=0.002). Her-2 positive patients had poor 10-year survival (P=0.041). A trend of low survival and high recurrence rate was observed in AR positive patients, but this was not significant (P=0.072). No statistically relevant correlations were seen in the case of ER and PR. In conclusion, Her-2 may be a valuable marker for predicting long-term prognosis of OSCC patients.

Methods
Data of 100 OSCC patients was collected retrospectively from patient medical records and subsequent follow-up visits at clinics. Patient demographics, risk factor usage history, clinical characteristics and survival were correlated with experimental data (biomarker expression). Overall survival (OS) (minimum follow up 60 months) and 10-year survival (minimum follow up 120 months) was taken as number of months from diagnosis until last follow-up (if alive) or date of death (if dead). Disease-free survival (DFS) was calculated as the number of months starting from surgery until date of recurrence or if no recurrence then until last follow-up (if alive) or date of death. SPSS version 19 (IBM, USA) was used for statistical analysis. Statistical tests included chi-square, Fisher's Exact test, logistic regression, Kaplan-Meier analysis and cox regression univariate analysis.

口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）占头颈部肿瘤的绝大多数，在巴基斯坦因普遍存在的口腔不良习惯，成为致死率居高的恶性肿瘤之一。生长因子受体与激素受体在部分癌症中可作为预后标志物及治疗靶点，但此类受体在OSCC中的应用尚有待探索。本研究旨在检测OSCC患者体内生长因子受体与激素受体的表达情况，并分析其与10年总生存期及无病生存期的相关性。为达成上述研究目标，本研究对100例福尔马林固定石蜡包埋的原发性OSCC组织标本进行了Her-2（人表皮生长因子受体2）、AR（雄激素受体）、ER（雌激素受体）及PR（孕激素受体）的免疫组化检测。研究人员将受体表达水平与患者口腔不良习惯、临床病理特征进行关联分析，并采用Kaplan-Meier法及Cox回归单因素分析对患者生存期进行评估。
本研究纳入的100例患者中，男性57例，女性43例。免疫组化结果显示，21%的患者存在Her-2免疫阳性表达，13%的患者AR阳性，3%的患者ER阳性，PR阳性率为0%。存在咀嚼槟榔果/槟榔嚼块口腔不良习惯的患者，Her-2阳性表达显著缺失（P=0.035）。此外，Her-2阴性患者的AR表达同样呈阴性（P=0.002）。Her-2阳性患者的10年生存期更差（P=0.041）。AR阳性患者呈现出生存期较短、复发率较高的趋势，但该差异未达到统计学显著性（P=0.072）。ER与PR的表达未发现具有统计学意义的相关关联。综上，Her-2或可作为预测OSCC患者长期预后的有效标志物。

研究方法
本研究回顾性收集了100例OSCC患者的临床病历资料及后续门诊随访数据。将患者的人口统计学特征、危险因素暴露史、临床特征及生存期数据与实验检测得到的生物标志物表达数据进行关联分析。总生存期（overall survival, OS）以确诊至末次随访（存活患者）或死亡日期（死亡患者）的月数计算，随访时长最低要求为60个月；10年生存期的随访最低要求为120个月。无病生存期（disease-free survival, DFS）的计算方式为：从手术之日起至复发日期止；若无复发，则截至末次随访（存活患者）或死亡日期。本研究采用SPSS 19.0版本（美国IBM公司）进行统计学分析，所用统计方法包括卡方检验、Fisher确切概率法、logistic回归、Kaplan-Meier分析及Cox回归单因素分析。