Szentkúti Gabriella, Dános Kornél, Brauswetter Diána, Kiszner Gergő, Krenács Tibor, Csákó László, Répássy Gábor, Tamás László
Department of Oto-Rhino-Laryngology, Jahn Ferenc South-Pest Hospital, 1st Köves Street, 1204, Budapest, Hungary,
Pathol Oncol Res. 2015 Jul;21(3):643-50. doi: 10.1007/s12253-014-9869-4. Epub 2014 Dec 31.
Head and neck squamous cell carcinomas (HNSCC) show diverse clinicopathological features and are mostly linked with poor outcome. In this study, we tested if the expression of tumor growth, cell cycle and basement membrane anchorage related biomarkers allow prognostic and clinicopathological stratification of HNSCC. Archived HNSCC samples from 226 patients included into tissue microarrays (TMA) were tested using immunohistochemistry. Histopathological evaluation and the analysis of immunostaining for EGFR, Ki67, p53, p16(ink4) and Collagen XVII proteins were carried out in digital whole slides. Statistical evaluation was carried out using Pearson's Chi-square test and Kaplan-Meier survival analysis. In the tested cohort, hypopharyngeal cancers had the least favorable, and glottic cancers had the most favorable prognosis. High Ki67 positive tumor cell fractions were associated with significantly worse prognosis and elevated rate of lymph node metastasis. Both Ki67 and EGFR expression correlated significantly with the tumor localization. Ki67 index was the highest in the hypopharyngeal region and it proved to be the lowest in the glottic region. EGFR expression was the highest in the oral cavity and the lowest in the glottic region. The survival rate of patients with p16(ink4)-negative cancer was significantly lower than of those with p16(ink4)-positive disease. A significant inverse correlation was found between histological grade and the prognosis of HNSCC. Our data support that elevated Ki67 positive proliferating cell fractions contribute to the unfavorable prognosis of hypopharyngeal cancers, while glottic cancers have the most favorable prognosis because of the lowest Ki67 expression rate.
头颈部鳞状细胞癌(HNSCC)具有多样的临床病理特征,且大多与不良预后相关。在本研究中,我们检测了肿瘤生长、细胞周期和基底膜锚定相关生物标志物的表达是否能对头颈部鳞状细胞癌进行预后和临床病理分层。使用免疫组织化学方法检测了纳入组织微阵列(TMA)的226例患者的存档头颈部鳞状细胞癌样本。在数字全切片上进行组织病理学评估以及对表皮生长因子受体(EGFR)、Ki67、p53、p16(ink4)和XVII型胶原蛋白蛋白的免疫染色分析。使用Pearson卡方检验和Kaplan-Meier生存分析进行统计学评估。在受试队列中,下咽癌预后最差,声门癌预后最好。高Ki67阳性肿瘤细胞分数与显著更差的预后以及更高的淋巴结转移率相关。Ki67和EGFR表达均与肿瘤定位显著相关。Ki67指数在下咽区域最高,在声门区域最低。EGFR表达在口腔最高,在声门区域最低。p16(ink4)阴性癌患者的生存率显著低于p16(ink4)阳性疾病患者。在头颈部鳞状细胞癌的组织学分级和预后之间发现显著的负相关。我们的数据支持,Ki67阳性增殖细胞分数升高导致下咽癌预后不良,而声门癌因Ki67表达率最低而预后最好。