Starzyńska Anna, Adamska Paulina, Sejda Aleksandra, Sakowicz-Burkiewicz Monika, Adamski Łukasz Jan, Marvaso Giulia, Wychowański Piotr, Jereczek-Fossa Barbara Alicja
Department of Oral Surgery, Medical University of Gdańsk, 7 Dębinki Street, 80-211 Gdańsk, Poland.
Department of Pathomorphology, University of Warmia and Mazury, 18 Żołnierska Street, 10-561 Olsztyn, Poland.
Life (Basel). 2020 Dec 3;10(12):325. doi: 10.3390/life10120325.
Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling pathway of phosphatidylinositol 3-kinase. The study group included 92 patients treated for OSCC at the University Clinical Centre in Gdańsk, Poland. Study was performed on formalin-fixed paraffin-embedded samples from primary OSCC. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and phosphatase and tensin homolog encoded on chromosome 10 (PTEN) protein expression was assessed by immunohistochemistry (IHC). gene copy number was analyzed using chromogenic and silver in situ hybridization where molecular probes are marked by chromogens and silver ions. PIK3CA IHC H-score ≥ 70 was found in 51.65% patients, and loss of PTEN protein was noticed in 31.46% cases. PIK3CA amplification was detected in 5 tumors. In the case of PTEN protein expression, there was an inverse correlation with the T stage of the primary tumor ( -0.243) and positive correlation with a 5-year survival ( 0.235). The number of copies of the gene was associated with the tumor grading ( 0.208). The present study shows that loss of PTEN protein and the grading ( 0.040), distant metastases ( 0.033), smoking ( 0.016), and alcohol abuse ( 0.042) were prognostic factors for the survival of patients with OSCC. In contrast, the presence of amplification and OSCC on the floor of the mouth resulted in a nearly six-fold increase in the risk of shortening survival ( 0.037). Our finding suggests a potential prognostic significance of PTEN loss and PIK3CA amplification in OSCC. Future studies are needed to confirm our results.
口腔鳞状细胞癌（OSCC）占口腔病变的95%。尽管OSCC的治疗有了进展，但结果仍不尽人意。迫切需要确定OSCC的新疗法。这种治疗的一个目标可能是磷脂酰肌醇3激酶信号通路。研究组包括在波兰格但斯克大学临床中心接受OSCC治疗的92名患者。对原发性OSCC的福尔马林固定石蜡包埋样本进行研究。通过免疫组织化学（IHC）评估磷脂酰肌醇-4,5-二磷酸3激酶（PIK3CA）和10号染色体上编码的磷酸酶和张力蛋白同源物（PTEN）的蛋白表达。使用显色原位杂交和银原位杂交分析基因拷贝数，其中分子探针用显色剂和银离子标记。51.65%的患者PIK3CA IHC H评分≥70，31.46%的病例出现PTEN蛋白缺失。在5个肿瘤中检测到PIK3CA扩增。在PTEN蛋白表达方面，与原发性肿瘤的T分期呈负相关（-0.243），与5年生存率呈正相关（0.235）。该基因的拷贝数与肿瘤分级相关（0.208）。本研究表明，PTEN蛋白缺失以及分级（0.040）、远处转移（0.033）、吸烟（0.016）和酗酒（0.042）是OSCC患者生存的预后因素。相比之下，口腔底部出现扩增和OSCC会使生存缩短风险增加近6倍（0.037）。我们的发现表明PTEN缺失和PIK3CA扩增在OSCC中具有潜在的预后意义。需要进一步的研究来证实我们的结果。
