ERβ mRNA expression in ERα-negative and triple-negative breast cancers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 574-574
Author(s):  
Young Choi ◽  
Hadong Kim ◽  
Tae-Hoon Kim
Keyword(s):  
Cyclin D1 ◽  
Mrna Expression ◽  
Triple Negative ◽  
Lymph Node Status ◽  
Mrna Levels ◽  
Nuclear Staining ◽  
Breast Cancers ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Reverse Transcription Pcr

574 Background: ERα is the main prognostic and therapeutic marker in breast cancer (BC). About 30% of BC cases are negative for ER (ERα-) and do not benefit from antiestrogen therapy (TAM). We aim to study ER-beta (ERβ) expression in ERα- and triple negative (TN) cancers to explore alternate pathway of treatment in this cohort. Methods: We studied 67 ERα- BC cases including 44 TN together with 74 ERα +BC cases obtained from patients aged 29 to 97 years old between 2003 and 2010. The histology included 110 intraductal, 12 medullary and 19 other types. 78 cases were grade 3, 52 were grade 2, and 11 were grade 1. RNA was extracted from FFPE and mRNA levels of ERβ isoform and ERα were determined by real-time quantitative reverse transcription PCR. IHC stains were done on TMA the sections for ERα, PR, Her-2, Ki-67, CK5/6 and Cyclin D1. Results: ERβ isoforms were highly expressed in ERα-, TN, basal-like and HER2 type BC cases. ERβ2 was the major ERβ variant expressed. Ki-67 proliferating cells (>20% nuclear staining) were mostly in ERα- rather than ERα+ cases (69.0% vs. 31.0%) as were cyclin D1- cells (82.2% vs. 17.8%). On the other hand, in ERα+ BC, ERα mRNA expression was consistently high and upregulated, and ERβ, low and down regulated, and the ratio of ERα+ to ERβ+ ranged from 3 to 100. ERβ1, 2 and 5 were co-expressed with ERα in 56%, 63%, and 30% of cases, respectively. Overall, ERβ mRNA levels did not show any significant correlation with age, tumor size, lymph node status and histological grades. Conclusions: ERβ-dependent proliferating tumor cells may render them more sensitive to TAM, and increase the effectiveness of TAM and its metabolites in ERα- and TN cases. Increased overall survival after adjuvant TAM ERα-BC may be directly related to ERβ over-expression. ERβ isoform is potential selective therapeutic target in a sub-cohort of ERα- BC. Additionally, when ERβ and ERα are co-expressed, ERβ appears to play a distinct role from its action in ERα- BC. [Table: see text]

Clinical significance of ERβ mRNA expression in ERα-negative and triple-negative breast cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 545-545
Author(s):  
Young Choi Kim ◽  
Hadong Kim ◽  
Tae-Hoon Kim
Keyword(s):  
Mrna Expression ◽  
Triple Negative ◽  
Myoepithelial Cells ◽  
P Value ◽  
Breast Cancers ◽  
Chi Square ◽  
Ki 67 ◽  
Kaplan Meier ◽  
Asco Meeting

545 Background: Previously at the 2012 ASCO meeting, we reported significant ERβ mRNA expression in ERα-negative (ERα-) and triple negative breast cancers (TNBC). In this study, we analyzed its clinical outcome and correlation with other clinical parameters. Methods: A total of 141 cases consisted of 69 ERα- BC including 41 TNBC and 72 ERα+ BC were obtained from patients aged 29 to 97 years old between 2003 and 2010. Treatments included surgery, hormone, chemo- or radiotherapy, or any combinations. The follow-up period ranged from 1 to 132 months. ERβ mRNA was analyzed from formalin-fixed tumor tissues by RT-PCR. ERα, PR, Her-2, Ki-67, AIB-1, NFk/p65, p-c-jun, Ki-67, TIF-2, SRC-1, CK5/6 and p53 were tested by immunohistochemistry. The correlation was deemed significant if p value less than 0.05 from Chi-square. Overall survival (SVR) was defined from the date of diagnosis to last follow-up or death attributed to BC and was analyzed by the Kaplan-Meier curves and Wilcoxon rank sum. Results: Single or combination of ERβ isoform(s) was highly expressed in both ERα- and TNBC and ERβ2 was the most frequent (48.8%) and ERβ5, the least (30.2%). In contrast, ERβ5 was the most frequent in ERα+BC. Presence of all or any ERβ isoform was associated with significantly higher SVR in all cases, and in TNBC (ERβ total, Wilcoxon p = 0.0177, ERβ2, p= 0.0329), and also with negative LN (p< 0.0001). ERβ2 and ERβ5 were expressed in 63.2% and 30 %, respectively, in 20 patients died in 1 to 60 months. Over expression of AIB-1, NF-kB/p65 and TIF-2 was associated with ERβ1 and ERβ2 (p<0.05). Ki-67 + cells were mostly ERβ + BC than ERα+. ERα mRNA expression was up-regulated, and ERβ,down- regulated, with the ERα: ERβ+ ratio of 3-1000:1. There was no association between ERβ expression and the stage, age, tumor size, and postmenopausal status. Conclusions: Specific ERβ isoform appears to be a significant discriminating factor for SVR and negative node. ERβ2 is the predominant isoform in ERα- but ERβ5 in ERα+BC, suggesting a distinct role of ERβ isoform in ERα- and ERα+BC. ERβ isoform may be a selective therapeutic target in this cohort. ERβ+/ Ki-67+cells appear to be a sub-population of BC arising from basal-myoepithelial cells in this cohort.

scholarly journals Expression of CD4, CD8 Biomarkers in Invasive Carcinoma of Breast with Clinicopathological Correlation

2021 ◽  
pp. 65-73
Author(s):  
C. Divyapriya ◽  
Aarthi Kannan ◽  
Vijayashree Raghavan
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Invasive Breast Cancer ◽  
Triple Negative ◽  
Invasive Carcinoma ◽  
Tumour Size ◽  
Breast Cancer Subtype ◽  
Lymph Node Status ◽  
Breast Cancers ◽  
Cd8 T Lymphocytes

Introduction: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in various cancers, including invasive breast cancer (IBC). Aim and Objectives: To correlate the expression of CD4, CD8 T-lymphocytes in invasive carcinoma breast with established markers of prognosis like tumour size, grade, lymph node status and molecular subtypes mainly ER, PR, Her 2Neu, Ki67 status, mainly the triple negative breast cancers(TNBC). Methodology: 58 Invasive breast carcinoma proven tissue blocks were subjected to immunohistochemistry and morphometric analysis for positive CD4, CD8 T-lymphocytes were done. Results:  Triple negative breast cancer subtype shows high TILs than other pathologic subtypes. Tumor interface CD8+ cells very well correlated with the pathological higher nodal stage. Majority CD4, CD8 positive cells were populated more towards the stromal and interface of the tumor microenvironment rather thatintratumoral. Conclusion: CD4+ and CD8+ counts may be a valuable independent prognostic tool in predicting the outcome in invasive breast cancer.

scholarly journals Evolutionary conservation in various mammalian species of the human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody.

1989 ◽  
Vol 37 (10) ◽  
pp. 1471-1478 ◽  
Author(s):  
B Falini ◽  
L Flenghi ◽  
M Fagioli ◽  
H Stein ◽  
R Schwarting ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
Mammalian Species ◽  
Calf Serum ◽  
Evolutionary Conservation ◽  
Resting Cells ◽  
Nuclear Staining ◽  
Proliferating Cells ◽  
Ki 67

The human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody (MAb) was detected in proliferating normal and neoplastic cells of many mammalian species (lamb, calf, dog, rabbit, rat) besides human. In contrast, Ki-67 stained proliferating cells from other species weakly (mouse) or not at all (swine, cat, chicken, pigeon). The immunostaining pattern of Ki-67 in animal tissues was identical to that previously described in human: Ki-67 reacted only with cells known to proliferate (e.g., germinal center cells, cortical thymocytes) but not with resting cells (e.g., hepatocytes, brain cells, renal cells); this MAb produced a characteristic nuclear staining pattern (e.g., stronger labeling of nucleoli than of the rest of the nuclei and staining of chromosomes in mitotic figures); and Ki-67 crossreacted with the squamous epithelium in both animal and human tissues. In vitro studies showed that when quiescent (Ki-67-negative) NIH 3T3 fibroblasts or bovine peripheral blood lymphocytes were induced to proliferate, the appearance of Ki-67-positive cells paralleled the induction of cell proliferation caused by addition of fetal calf serum or PHA, respectively, to the cultures, and in both human and rat proliferating cells the Ki-67 expression closely paralleled the incorporation of [3H]-thymidine. These findings indicate that the epitope recognized by the Ki-67 MAb in human and animal species is the same. The widespread evolutionary conservation of the human proliferation-associated epitope recognized by the Ki-67 MAb suggests that it and/or its carrier molecule may play an important role in regulation of cell proliferation.

Clinicopathologic characteristics of triple-negative breast cancer and relationship to basal markers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11519-e11519
Author(s):  
Dimitrios Tryfonopoulos ◽  
Georgios Oikonomopoulos ◽  
Stamatina Demiri ◽  
Lazaros Lekakis ◽  
Nikolaos Fragkiskos Pistamaltzian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Stage Iv ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics ◽  
Ki 67 ◽  
Immunohistochemical Markers ◽  
Gene Expression Studies

e11519 Background: Triple negative breast cancers are immunohistochemical surrogates of basal-like breast cancers. There is no complete overlap between triple negative and basal-like tumors and as gene expression studies evolve, further subclassification bearing clinical relevance is underway. Our purpose was to correlate clinicopathologic characteristics of triple negative breast cancer tumors with expression of basal markers in an effort to define immunohistochemically subgroups of this heterogenous disease Methods: Data were retrieved and analysed using our electronic databank. Patient samples were reviewed by an expert breast cancer pathologist and stained additionally for EGFR and CK 5/6 antibodies. Results: Sixty-five women with triple negative breast cancer were identified. Mean age was 58.3±12.9 years. Most tumors (86%) were of ductal histology, 53% grade 3, 48% having high Ki-67 index (>14%). 10% of patients presented with Stage IV, 25% with Stage III, 38% with stage II and 27% with stage I disease. 63% of patients were postmenopausal. EGFR staining was present in 43% of tumor samples, whereas CK 5/6 in 38.5%. Both EGFR and CK 5/6 expression was found in 18.5%, whereas 37% of tumors expressed neither EGFR or CK 5/6. No difference was observed between tumors expressing any of these 2 basal markers as compared to EGFR and CK 5/6 negative tumors in terms of Ki-67 index, grade, tumor size and nodal involvement. Lymphovascular invasion and non-ductal histology tended to occur more frequently (p=ns) in non-basal tumors. Additionally, patients with expression of any of the basal markers tended to be more obese than the non-basal triple negative breast cancer patients (p=ns). Conclusions: Further immunohistochemical markers apart from EGFR and CK 5/6 are needed in order to further define clinically meaningful subgroups of triple negative breast cancer.

High mRNA expression of LMO4, a BRCA1 downregulator, correlates with better prognosis in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18137-e18137
Author(s):  
Santiago Viteri Ramirez ◽  
Carlota Costa ◽  
Ana Gimenez Capitan ◽  
Susana Benlloch ◽  
Miquel Taron ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Negative Regulator ◽  
Egfr Mutations ◽  
Mrna Levels ◽  
Breast Cancers ◽  
T790m Mutation ◽  
Low Levels ◽  
The Impact

e18137 Background: Advanced NSCLC p with EGFR activating mutations show an impressive progression-free survival (PFS) to erlotinib. The co-existence of the EGFR T790M mutation, in conjunction with high BRCA1 mRNA levels, affected PFS to erlotinib (Rosell et al. CCR 2011). LMO4 is a negative regulator of BRCA1 function in sporadic breast cancers, and CtIP can bind to BRCA1 and LMO4. We have assessed the expression of CtIP, LMO4 and BRCA1 and examined the impact of CtIP and LMO4 levels on outcome. Methods: mRNA expression of LMO4 and CtIP was examined by RT-PCR in the original pretreatment tumor biopsies of 81 NSCLC p with sensitive EGFR mutations. Results: Expression of BRCA1 and LMO4 was successfully assessed in 55 p: median age, 68; 61.8% female; 98.2% Caucasian; 63.6% never-smokers; 81.8% ECOG PS <2; 80% adenocarcinoma; 14.5% BAC; 4.5% LCC; 94.5% stage IV; 63.6% exon 19 deletion; 36.4% L858R mutation; 36.4% T790M; 83.1% showed clinical benefit to erlotinib (CR/PR/SD). BRCA1 expression was correlated with that of CtIP (r=0.31; P=0.01) and LMO4 (r=0.32; P=0.02). There was no correlation between CtIP and LMO4 (r=0.09; P=0.49). PFS for p with high LMO4 levels was not reached while it was 13 months (m) for p with low levels (P=0.006). Overall survival (OS) was not reached for p with high levels of LMO4 and was 31 m for p with low levels (P=0.17). No differences in PFS or OS were observed according to CtIP levels. When BRCA1 and LMO4 expression was analyzed together, PFS was not reached for p with low BRCA1 and high LMO4 levels and was 19 m for p with low levels of both genes (P=0.04). PFS was 8 m for p with high BRCA1 and low LMO4 levels and 18 m for p with high levels of both genes (P=0.03). In the multivariate analysis, BRCA1 and LMO4 expression emerged as markers of PFS (Table). Conclusions: BRCA1 and LMO4 mRNA expression can predict PFS to erlotinib in p with EGFR mutations and could be useful in the development of new therapeutic strategies. [Table: see text]

Claudin 1, 3, 4, and 7 expression in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1070-1070
Author(s):  
Beom Seok Ko ◽  
Hee Jeong Kim ◽  
Jong Han Yu ◽  
jong Won Lee ◽  
Byung Ho Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Lymph Node Status ◽  
High Recurrence Rate ◽  
Breast Cancers

1070 Background: Triple negative breast cancer (TNBC) often grows rapidly and has poor prognosis, with a high recurrence rate. Because conventional endocrine treatment and HER2 targeted therapy for TNBC is invalid, chemotherapy is the only systemic treatment for TNBC. It is known that several subtypes within the TNBC show different responses to chemotherapy, depending on the subtypes. Recently, a claudin (CLDN) low breast cancer has been identified, exhibiting low expressions of CLDNs 1, 3, 4 and 7. CLDNs are transmembrane proteins that seal tight junctions and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Methods: Surgically removed, formalin-fixed, paraffin-embedded breast cancers from 341 TNBC patients were analyzed to identify CLDN expression.They underwent wide local excision or mastectomy between March, 2004 and December, 2007 at the breast surgery unit of Asan Medical Central Hospital. Results: In our tumor series, we found 45.0% (153/339) of high expressing cases for CLDN1, 57.0% (192/337) for CLDN3, 57.6% (194/337) for CLDN4 and 44.0% (149/339) for CLDN7. Overall, we found 20.5% (70/341) of cases were within the low CLDN expression group and 79.5% (271/341) of tumors were within the high expression group of CLDN1, 3, 4 ,7. Although the high CLDN expression group was significantly associated with positive lymph node status and higher stage, there were no significant differences between CLDN low and high groups in disease free survival (p=0.477) or overall survival (p=0.253). Conclusions: CLDN high tumors are associated with poor prognosis features, but they are not an independent prognostic factor in TNBC patients. However, the mechanisms underlying the different roles of CLDNs in tumorigenesis are largely unclear. Studying the associations of these CLDNs with the TNBC subgroup of breast cancers might provide us with potential diagnostic biomarkers or therapeutic targets for cancer cells.

Relationship of ERCC1 genotype variant with mRNA expression and ERCC1 protein levels in advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 260-260
Author(s):  
Elizabeth A. Guancial ◽  
Lillian Werner ◽  
Joaquim Bellmunt ◽  
Nikitas Nikitas ◽  
Edward C. Stack ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Excision Repair ◽  
Predictive Biomarker ◽  
Mrna Levels ◽  
Nuclear Staining ◽  
Protein Levels ◽  
Tissue Arrays ◽  
Platinum Based Chemotherapy ◽  
The Relationship

260 Background: DNA repair factors may be predictive for response to chemotherapies that produce DNA damage. While low ERCC1 protein and mRNA levels have been reported as associated with improved outcomes in metastatic UC patients treated with platinum-based chemotherapy, the relationship between genotype, mRNA expression, and protein level is unknown. The ERCC1 germline 19007C>T single-nucleotide polymorphism (SNP) is functionally associated with reduced translation of ERCC1 mRNA. We investigated the relationship between ERCC1 germline SNP, ERCC1 tumor mRNA and protein expression, in a cohort of patients with advanced UC who received first-line, platinum-based chemotherapy. Methods: A cohort of clinically annotated, uniformly-treated advanced UC patients with FFPE primary tumor tissue available was identified through the Hellenic cooperative Oncology Group (HECOG) (N=93). Genomic DNA extraction, nested PCR, and restriction fragment length polymorphism techniques for the 19007C>T SNP were performed to identify C/C, C/T and T/T genotypes. ERCC1 mRNA expression was interrogated using Nanostring nCounter profiling. IHC analysis was performed on tissue arrays using an ERCC1 antibody. Percent of positive nuclear staining was categorized as quartiles using previously identified cut-points. Results: ERCC1 C/T genotype was identified in 30/61 samples (49%) and T/T in 14/61 samples (23%). In 54 patients with both SNP and mRNA data available, T/T genotype was associated with the highest level of mRNA expression, followed by the C/T genotype (p=0.04). Neither ERCC1 genotype (N=44) nor ERCC1 mRNA expression (N=54) was associated with ERCC1 protein expression as measured by IHC (p=0.52 and p=0.13, respectively). Conclusions: ERCC1 19007C>T is associated with increased ERCC1 mRNA expression. However, neither genotype nor mRNA are surrogates for ERCC1 protein detected by IHC in advanced UC tumors. This suggests that while genotype influences mRNA expression of ERCC1, the use of the nucleotide excision repair pathway as a predictive biomarker of platinum-sensitivity may be more complex than previously appreciated and require the integrative use of proteomics, genomics and epigenomics.

scholarly journals ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Primary Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.

The role of Ki-67 in Asian triple negative breast cancers: a novel combinatory panel approach

2019 ◽  
Vol 475 (6) ◽  
pp. 709-725 ◽  
Author(s):  
An Sen Tan ◽  
Joe Poe Sheng Yeong ◽  
Chi Peng Timothy Lai ◽  
Chong Hui Clara Ong ◽  
Bernett Lee ◽  
...  
Keyword(s):  
Triple Negative ◽  
Breast Cancers ◽  
Ki 67

Clinicopathologic characteristics of HER2-positive metaplastic squamous cell carcinoma of the breast

2020 ◽  
pp. jclinpath-2020-206468
Author(s):  
Ting Lei ◽  
Tianjie Pu ◽  
Bing Wei ◽  
Yingying Fan ◽  
Libo Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Lymph Node Status ◽  
Her2 Positive ◽  
Ki 67

AimsThe aim of this study was to analyse the clinicopathological features and prognosis of human epidermal growth factor receptor-2 (HER2)-positive metaplastic squamous cell carcinoma (MSCC).MethodsFifty-eight patients with MSCC of the breast who were classified into 45 triple-negative and 13 HER2-positive subgroups diagnosed at the West China Hospital, Sichuan University, from 2004 to 2018, were enrolled. Clinicopathological features were collected and compared between HER2-positive MSCC, triple-negative MSCC, HER2-positive invasive breast carcinoma of no special type (NST) and triple-negative NST groups. In the prognostic survival analysis, HER2-positive MSCCs was compared with triple-negative MSCCs, HER2-positive NSTs and triple-negative NSTs.ResultsCompared with triple-negative MSCCs, more patients with Ki-67 low expression were in HER2-positive MSCCs (p<0.05). More patients with HER2-positive MSCC than patients with HER2-positive NST were postmenopausal (p<0.05). Compared among HER2-positive MSCCs, triple-negative MSCCs and triple-negative NSTs, patients of HER2-positive MSCCs with high Ki-67 expression were the least, and HER2-positive MSCCs had more strongly associated with postmenopausal disease status (p<0.05). In survival analyses, HER2-positive MSCCs had a high risk of recurrence and poor prognosis (p<0.05). Lymph node status was significantly associated with the disease-free survival of patients with HER2-positive MSCC.ConclusionIn conclusion, our study indicates that HER2-positive MSCC is an aggressive disease with unique clinicopathological characteristics. Both HER2-positive status and an SCC component are critical factors for poor prognosis. HER2-positive MSCC and triple-negative MSCC are distinct subgroups. Corresponding targeted therapy recommendations should be made for this HER2-positive MSCC group.

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