Clinicopathological Analysis Of Triple Negative Breast Cancer And The Significance Of TRPS1 And GATA-3 In Its Pathological Diagnosis

Objective:To analyze the clinicopathological characteristics and overall survival rate of triple-negative breast cancer(TNBC),and explore the possible factors affecting prognosis;the histological classification of TNBC and its relationship with clinical pathological features;To detect the expression of TRPS1 and GATA-3 in TNBC,to analyze the correlation between TRPS1 and GATA-3 and clinicopathological characteristics,and to explore more sensitive markers to judge the origin of TNBC.Methods:A total of 246 TNBC specimens that underwent surgical resection at Qilu Hospital of Shandong University from January 1,2015 to January 31,2020 were collected,while 76 TNBC lymph node metastasis samples and 17 distant metastasis samples were included as a validation queue.Clinicopathological characteristics and histological types of the 246 TNBC were analyzed,and clinicopathological characteristics parameters including patient age,tumor size,metastasis to lymph nodes,TNM stage,histological grade,and proliferation index of Ki-67 expression were evaluated.Survival rates were estimated using the Kaplan-Meier method in parallel with univariate analysis,and the effect of clinicopathological parameters on survival was examined using a Cox proportional hazards model.The TIMER and UALCAN databases were used to analyze the expression of TRPS1 and the breast origin markers of GATA-3,GCDFP-15 and mammaglobin in the tumor spectrum.Immunohistochemical staining of primary TNBC foci,lymph node metastases,and distant metastases was used to detect TRPS1 and GATA-3 expression.All analyses were performed using SPSS 26.0 software and a P-value<0.05 indicated that the results were statistically different.Result:1.Clinicopathological characteristics and survival analysis of TNBC:The median age of TNBC patients was 53 year-old(between 29 and 94 year-old),and about 40.7%of patients were ≤50 years old at onset.TNM stage was predominantly early,85.3%were stage Ⅰ-Ⅱ;Tumor diameter was predominantly ≤5 cm(96.7%);About 64.2%of patients were without lymph node metastasis at diagnosis;Histological grade was predominant in 3 cases(82.9%)and was grade 1 in only 5 cases(2.0%);The Ki-67 index of tumor tissues was higher,and approximately 85.8%of those with≥30%positive rate.Of 246 patients,134 were treated with postoperative chemotherapy,of whom 24 were treated with upfront radiation based on chemotherapy,19 patients were died,11 progressed to distant metastasis,and 2 recurred.With a median follow-up time of 53.0 months,the OS rates at 1 and 3 years were 98.8%,and 88.7%,respectively.Tumor size,lymph node metastasis status,and TNM stage were the main factors affected the prognosis.2.Histological subtypes of TNBC and their association analysis with clinicopathological features:a total of 246 TNBC were classified into six histological subtypes,including 221 cases of invasive breast carcinoma(non-special type),10 cases of metaplastic carcinoma,10 cases of breast carcinoma with apocrine differentiation,3 cases of invasive lobular carcinoma,1 case of invasive micropapillary carcinoma and 1 case of adenoid cystic carcinoma.Invasive breast cancer(non-special type)included 27 cases of invasive carcinoma with medullary features,4 cases of glycogen-rich clear cell carcinoma,2 cases of lipid-rich carcinoma,and 1 case of polymorphous carcinoma;Metaplastic carcinoma can be further divided into 3 cases of fibromatosis like metaplastic carcinoma,3 cases of squamous cell carcinoma,3 cases of stroma producing carcinoma,and 1 case of myoepithelial carcinoma.The Ki-67 index and histological grade were higher in the non-special subtype compared with the special subtype(P<0.001),and no differences were found between them in clinicopathological parameters such as TNM stage or tumor size.Although there was no significant difference in the 3-year OS rates between the special subtype and non-specific subtype(P>0.05),most of the 19 patients who died were from the non-specific subtype,only two were from the special subtype,and none of the patients who died from invasive apocrine carcinoma,invasive lobular carcinoma,adenoid cystic carcinoma,and fibromatosis like metaplastic carcinoma in the special subtype,the above results suggest that the special type of TNBC has a better prognosis.3.Database analysis of the expression of TRPS 1 and the breast epithelial derived markers of GATA-3,GCDFP-15,and mammaglobin:The TIMER and UALCAN databases show that Trpsl is highly expressed only in breast cancer among different types of cancers and that it is highly expressed in different molecular subtypes of breast cancer including luminal A,luminal B,HER2 overexpression,and basal-like subtypes.However,GATA-3,GCDFP-15,and mammaglobin,in addition to their relatively high expression in breast cancer,are also expressed in other tumor,and their expression is higher in luminal A,luminal B,and HER2 overexpression breast cancers than that in the basal-like subtype.4.Expression of TRPS 1 and GATA-3 protein in TNBC tissues:In the primary and lymph node metastasis groups,the TRPS1 protein-positive rates were 95.1%(234/246),89.5%(68/76),and GATA-3 protein-positive rates were 47.6%(117/246),39.5%(30/76),respectively.The positive rates of the combination were 96.3%,and 93.4%in the primary tumor and lymph node metastases,respectively.The kappa test for concordance showed that there was no concordance between the TRPS1 and GATA-3 expression intensities among the primary,lymph node,or metastasis groups(P>0.05).The results of the nonparametric rank-sum test showed that the expression of TRPS1 was higher than that of GATA-3 in either the TNBC primary or lymph node metastasis groups(P<0.05).5.Expression of TRPS 1 and GATA-3 in distant metastatic focal TNBC tissues:Among the 17 TNBC tissues with distant metastasis visits and later confirmed breast cancer as the primary site,the positive rates of TRPS1 and GATA-3 were 94.1%(16/17),29.4%(5/17),respectively,and the kappa concordance test and nonparametric rank-sum test showed that the positive rate of TRPS 1 was significantly higher than that of GATA-3(P>0.05);When both were combined,the positive rate was 94.1%.The results suggest that either TRPS1 alone or the combination of TRPS1 and GATA-3 will be important to examine whether metastatic tumors of unknown origin are of breast cancer origin.Conclusion:1.Patients with TNBC ranged in age from 29 to 94 years,with a median age of 53 years;By the time of surgery,tumors were smaller than 5 cm in diameter;TNM stage was mainly stage Ⅰ and Ⅱ;Histological grade was mainly grade 3;Ki-67 proliferation index was high.Tumor size,lymph node involvement status,and TNM stage are major prognostic factors in TNBC,especially lymph node involvement status.2.The histology of TNBC included invasive breast cancer(non-specified type)in 221 cases;Invasive breast cancer(non-specified type)was further classified as classic(187 cases),invasive carcinoma with medullary features(27 cases),glycogen-rich clear cell carcinoma(4 cases),lipid-rich carcinoma(2 cases),pleomorphic carcinoma(1 case);Special types included invasive apocrine carcinoma(10 patients),invasive lobular carcinoma(3 patients),metaplastic carcinoma(10 patients),invasive micropapillary carcinoma(1 patient),adenoid cystic carcinoma(1 patient);Metaplastic carcinomas included fibromatosis like metaplastic carcinoma(3 cases),squamous cell carcinoma(3 cases),stromal producing carcinoma(3 cases),and myoepithelial carcinoma(1 case).Despite the multitude of histological subtypes of TNBC,the most predominant subtype remains invasive breast cancer(non-specified type).3.The special type had lower expression and histological grade of proliferation index Ki-67 than the non-special type;Only 2 of the deceased cases were from special cases,and none of the patients with invasive apocrine carcinoma,invasive lobular carcinoma,adenoid cystic carcinoma,and fibromatosis-like metaplastic carcinoma presented deceased cases,indicating a better prognosis in the special subtype.4.Database analysis showed that TRPS1 was more specific than GATA-3,GCDFP-15,and mammaglobin as breast cancer markers;Immunohistochemistry results showed that TRPS1 was more highly expressed and more strongly expressed than GATA-3 in TNBC.TRPS1 is a more sensitive marker of mammary origin.5.For metastatic tumors in which the primary site could not be identified,immunohistochemical results showed positivity for TRPS1 and(or)GATA-3 expression,they were strongly suggestive of a TNBC origin.In the daily routine,TRPS1 alone or in combination with GATA-3 can be used to increase the detection rate of breast cancer,especially TNBC.