PD-L1在头颈部高分化鳞状细胞癌中的表达模式及临床病理学意义

Expression pattern and clinicopathological significance of PD-L1 in highly differentiated head and neck squamous cell carcinoma

目的:研究高分化头颈部鳞状细胞癌(HNSCC)中程序性死亡受体配体1(PD-L1)的表达情况、肿瘤浸润淋巴细胞(TILs)的分布及临床病理特征。方法:回顾性分析127例高分化HNSCC手术患者的临床病理资料,采用IHC检测PD-L1在癌组织、不典型增生组织及癌旁正常组织中的表达,HE镜下评估TILs的分布情况。结果:PD-L1在高分化鳞状细胞癌的癌细胞或TILs高表达(CPS≥20,约占69.3%)或低表达(1≤CPS<20,约占30.7%);在不典型增生组织中不表达(CPS<1,约占29.9%)或低表达(1≤CPS<20,约占69.2%),个别病例高表达(CPS≥20,约占0.9%);在癌旁正常组织中不表达(CPS<1,约占56%)或散在隐窝上皮或极少数淋巴细胞低表达(CPS=1约占22%;CPS=2约占16%;CPS=5约占6%),差异有统计学意义(P=0.000)。TILs在高分化鳞状细胞癌的癌组织中主要呈重度浸润(低度浸润约占7%,中度浸润约占38.6%,重度浸润约占54.3%);在不典型增生组织中主要呈中度浸润(低度浸润约占5.6%,中度浸润约占52.3%,重度浸润约占42.1%);在癌旁正常组织中主要呈低度浸润(低度浸润约占88%,中度浸润约占11%,重度浸润约占1%);差异有统计学意义(P=0.000)。高分化鳞状细胞癌的癌组织中PD-L1的表达与肿瘤浸润淋巴细胞(TILs)呈正相关(P=0.018)。在表达模式上,PD-L1在癌旁正常组织中不表达或少数表达于隐窝上皮及周围淋巴细胞;在不典型增生组织中不表达或低表达于上皮的基底部及周围淋巴细胞;在极高分化鳞状细胞癌(4例疣状癌)及早期浸润性癌,主要表达于浸润前沿的癌细胞,表达部位有明显的极向性;在广泛浸润的鳞状细胞癌中PD-L1表达极向性不明显。癌组织中TILs多聚集围绕在浸润性癌巢周围,PD-L1高表达。癌旁正常组织中淋巴细胞少,其中仅见极少数PD-L1阳性的淋巴细胞。结论:PD-L1和TILs在高分化鳞状细胞癌中高表达及其相关性,反映了肿瘤浸润过程与肿瘤微环境的相互作用,其特征性的形态模式可能为高分化浸润性癌的诊断提供线索;PD-L1在头颈部高分化鳞状细胞癌的癌组织中表达率高,高于不典型增生组织,明显高于癌旁正常组织,说明PD-L1可能促进了HNSCC的发生、发展过程。

Objective:To study the expression of programmed death receptor ligand 1(PD-L1),the distribution of tumor infiltrating lymphocytes(TILs)and the clinicopathological characteristics in highly differentiated head and neck squamous cell carcinoma(HNSCC).Methods:The clinicopathological data of 127 patients with highly differentiated HNSCC were retrospectively analyzed.The expression of PD-L1 in cancer tissue,atypical hyperplasia tissue and normal tissues adjacent to cancer was detected by IHC,and the distribution of TILs was evaluated under HE microscope.Results:PD-L1 was highly expressed(CPS≥20,accounting for 69.3%)or lowly expressed(1≤CPS<20,accounting for 30.7%)in cancer cells or TILs of highly differentiated squamous cell carcinoma.PD-L1 had no expression(CPS<1,accounting for 29.9%)or low expression(1≤CPS<20,accounting for 69.2%)in atypical hyperplasia tissues,and high expression(CPS≥20,accounting for 0.9%)in individual cases.There was no expression in normal tissues adjacent to cancer(CPS<1,accounting for about 56%)or scattered in crypt epithelium or very few lymphocytes with low expression(CPS=1,accounting for about 22%.CPS=2,accounting for about 16%.CPS=5,accounting for about 6%),and the difference was statistically significant(P=0.000).TILs in highly differentiated squamous cell carcinoma mainly showed severe invasion(low invasion accounted for 7%,moderate invasion accounted for 38.6%,and severe invasion accounted for 54.3%).In atypical hyperplastic tissues,it mainly presented moderate infiltration(low infiltration accounted for 5.6%,moderate infiltration accounted for 52.3%,and severe infiltration accounted for 42.1%).In normal tissues adjacent to cancer,it mainly presented low degree infiltration(low degree infiltration accounted for 88%,moderate infiltration accounted for 11%,and severe infiltration accounted for 1%).The difference was statistically significant(P=0.000).The expression of PD-L1 in highly differentiated squamous cell carcinoma was positively correlated with tumor infiltrating lymphocytes(TILs)(P=0.018).In terms of expression pattern,PD-L1 was not expressed in normal tissues adjacent to cancer or a few were expressed in crypt epithelium and peripheral lymphocytes.In atypical hyperplastic tissues,it is not expressed or low expressed in the basal part of the epithelium and peripheral lymphocytes.In highly differentiated squamous cell carcinoma(4 cases of verrucous carcinoma)and early invasive carcinoma,the expression was mainly in the cancer cells at the front of invasion,and the expression site had obvious polarity.The polarity of PD-L1 expression was not obvious in extensively infiltrating squamous cell carcinoma.TILs in cancer tissue mostly gathered around the infiltrating tumor nest,and PD-L1 was highly expressed.There are few lymphocytes in normal tissues adjacent to cancer,and only a few PD-L1 positive lymphocytes can be seen.Conclusion:The high expression and correlation of PD-L1 and TILs in highly differentiated squamous cell carcinoma reflect the interaction between tumor invasion process and tumor microenvironment,and their characteristic morphological patterns may provide clues for the diagnosis of highly differentiated infiltrating carcinoma.The expression rate of PD-L1 in highly differentiated squamous cell carcinoma of the head and neck is high,higher than that in atypical proliferative tissue and significantly higher than that in normal tissues adjacent to the cancer,indicating that PD-L1 may promote the occurrence and development of HNSCC.