乳腺化生性癌中肿瘤基质浸润淋巴细胞和PD-L1表达的临床意义OA

Objective:Most patients with metaplastic breast carcinoma(MBC)lack expression of hormone receptors and human epidermal growth factor receptor(Her)-2,are insensitive to radiotherapy and chemotherapy,and have a poorer prognosis than those with invasive breast carcinoma of no special type(IBC-NST)at the same stage.Therefore,there is an urgent need to identify new therapeutic strategies to improve patient outcomes.This study aims to evaluate the prognostic value and immunotherapy-guiding role of stromal tumor-infiltrating lymphocytes(sTILs)and programmed death-ligand 1(PD-L1)expression in MBC. Methods:Surgical specimens from 40 patients with MBC treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2016 to December 2023 were collected.Hematoxylin-eosin staining was used to assess the percentage of sTILs infiltration.Immunohistochemistry was performed to detect PD-L1 expression in tumor cells(TcPD-L1)and stromal immune cells(IcPD-L1).The infiltration and expression patterns were analyzed across different pathological subtypes and metaplastic components of MBC,and their associations with treatment and prognosis were evaluated. Results:Among the included MBC cases,the combined proportion of high/intermediate sTILs infiltration(H/I)was 42.5%(17/40).The positive expression rates of IcPD-L1 and TcPD-L1 were 52.5%(21/40)and 37.5%(15/40),respectively.The percentages of sTILs infiltration were significantly associated with IcPD-L1 positivity(χ2=12.841,P=0.001),but not with TcPD-L1 positivity(χ2=2.874,P=0.275).Among pathological subtypes,sTILs(H/I)was highest in squamous cell carcinoma(SCC)(64.7%,11/17)and lowest in MHM(16.7%,1/6),with a statistically significant difference(P<0.05).Among different metaplastic components,sTILs(H/I)was highest in SCC(33.3%,2/6)and lowest in SPC(22.2%,2/9),with no significant difference(P>0.05).The IcPD-L1 positivity rate was highest in SCC(76.5%,13/17)and lowest in MHM(33.3%,2/6),while TcPD-L1 positivity was highest in SCC(70.6%,12/17)and lowest in MMC(11.1%,1/9).There was no significant difference in IcPD-L1 positivity between SCC and MHM(P>0.05),whereas TcPD-L1 positivity differed significantly between SCC and MMC(P<0.05).Across metaplasia components,both IcPD-L1 and TcPD-L1 positivity rates were highest in SCC(66.7%and 50.0%,respectively)and lowest in SPC(44.4%and 33.3%,respectively),with no statistically significant differences(P>0.05).Univariate and multivariate analyses of overall survival(OS)and recurrence-free survival(RFS)showed that patients with sTILs(H/I)had better prognosis(P<0.05),while patients with sTILs(L)/IcPD-L1(+)had worse prognosis than those with sTILs(L)/IcPD-L1(-)(P<0.05).In 10 cases receiving neoadjuvant chemotherapy,comparison between preoperative biopsy and postoperative specimens showed a concordance rate of 100%for sTILs,and 70%and 90%for IcPD-L1 and TcPD-L1,respectively.In all discordant cases,PD-L1 expression was negative in biopsy specimens but positive in postoperative specimens after neoadjuvant chemotherapy. Conclusion:Different pathological subtypes of MBC have different tumor immune microenvironments,and the combined detection of TILs and PD-L1 can provide theoretical basis for clinical immunotherapy and prognosis prediction.