Anna Sokolova, Vaibhavi Joshi, Haarika Chittoory, Michael Walsh, Malcolm Lim, Jamie R Kutasovic, Kaltin Ferguson, Peter T Simpson, Sunil R Lakhani, Amy E McCart Reed
{"title":"ROS1免疫组化作为乳腺癌ROS1靶向治疗的潜在预测生物标志物：抗体克隆选择的影响","authors":"Anna Sokolova, Vaibhavi Joshi, Haarika Chittoory, Michael Walsh, Malcolm Lim, Jamie R Kutasovic, Kaltin Ferguson, Peter T Simpson, Sunil R Lakhani, Amy E McCart Reed","doi":"10.1111/his.15465","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Invasive lobular carcinoma (ILC) may show targetable vulnerabilities secondary to the characteristic loss of the cell adhesion protein E-cadherin. Specifically, a synthetic lethal interaction was identified between E-cadherin loss and ROS1 inhibition. Several clinical trials are currently under way to assess the efficacy of ROS1 inhibitors in ILC; however, ROS1 expression has not been confirmed in ILC tumours and ROS1 has not been validated as a biomarker in the breast cancer setting. This study aimed to (i) examine ROS1 expression in a large cohort of breast cancer cases and (ii) investigate the biology and clinical significance of ROS1 positivity in breast cancer.</p><p><strong>Methods and results: </strong>ROS1 immunohistochemistry was performed on a large cohort of ILC (n = 274) and invasive carcinoma of no special type (NST; n = 431) cases with extensive clinicopathological data. The staining performance of four ROS1 antibody clones was compared. There was marked variation in ROS1 status according to antibody clone. D4D6 and SP384 were negative in almost all breast cancer cases, whereas EP282 and EPMGHR2 were positive in 37 and 47% of ILC cases, and 49 and 74% of NST cases, respectively. Only data from clones D4D6 and SP384 were highly concordant, while EP282 and EPMGHR2 were positive in distinct breast cancer subtypes.</p><p><strong>Conclusions: </strong>Assessment of ROS1 status in breast cancer appears to be highly antibody clone-dependent. ROS1 antibody clone selection will be an important consideration in the design of clinical trials investigating the clinical validity of ROS1 as a predictive biomarker in breast cancer.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ROS1 immunohistochemistry as a potential predictive biomarker for ROS1-targeted therapy in breast cancer: impact of antibody clone selection.\",\"authors\":\"Anna Sokolova, Vaibhavi Joshi, Haarika Chittoory, Michael Walsh, Malcolm Lim, Jamie R Kutasovic, Kaltin Ferguson, Peter T Simpson, Sunil R Lakhani, Amy E McCart Reed\",\"doi\":\"10.1111/his.15465\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Invasive lobular carcinoma (ILC) may show targetable vulnerabilities secondary to the characteristic loss of the cell adhesion protein E-cadherin. Specifically, a synthetic lethal interaction was identified between E-cadherin loss and ROS1 inhibition. Several clinical trials are currently under way to assess the efficacy of ROS1 inhibitors in ILC; however, ROS1 expression has not been confirmed in ILC tumours and ROS1 has not been validated as a biomarker in the breast cancer setting. This study aimed to (i) examine ROS1 expression in a large cohort of breast cancer cases and (ii) investigate the biology and clinical significance of ROS1 positivity in breast cancer.</p><p><strong>Methods and results: </strong>ROS1 immunohistochemistry was performed on a large cohort of ILC (n = 274) and invasive carcinoma of no special type (NST; n = 431) cases with extensive clinicopathological data. The staining performance of four ROS1 antibody clones was compared. There was marked variation in ROS1 status according to antibody clone. D4D6 and SP384 were negative in almost all breast cancer cases, whereas EP282 and EPMGHR2 were positive in 37 and 47% of ILC cases, and 49 and 74% of NST cases, respectively. Only data from clones D4D6 and SP384 were highly concordant, while EP282 and EPMGHR2 were positive in distinct breast cancer subtypes.</p><p><strong>Conclusions: </strong>Assessment of ROS1 status in breast cancer appears to be highly antibody clone-dependent. ROS1 antibody clone selection will be an important consideration in the design of clinical trials investigating the clinical validity of ROS1 as a predictive biomarker in breast cancer.</p>\",\"PeriodicalId\":13219,\"journal\":{\"name\":\"Histopathology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-05-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Histopathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/his.15465\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Histopathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/his.15465","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
ROS1 immunohistochemistry as a potential predictive biomarker for ROS1-targeted therapy in breast cancer: impact of antibody clone selection.
Aims: Invasive lobular carcinoma (ILC) may show targetable vulnerabilities secondary to the characteristic loss of the cell adhesion protein E-cadherin. Specifically, a synthetic lethal interaction was identified between E-cadherin loss and ROS1 inhibition. Several clinical trials are currently under way to assess the efficacy of ROS1 inhibitors in ILC; however, ROS1 expression has not been confirmed in ILC tumours and ROS1 has not been validated as a biomarker in the breast cancer setting. This study aimed to (i) examine ROS1 expression in a large cohort of breast cancer cases and (ii) investigate the biology and clinical significance of ROS1 positivity in breast cancer.
Methods and results: ROS1 immunohistochemistry was performed on a large cohort of ILC (n = 274) and invasive carcinoma of no special type (NST; n = 431) cases with extensive clinicopathological data. The staining performance of four ROS1 antibody clones was compared. There was marked variation in ROS1 status according to antibody clone. D4D6 and SP384 were negative in almost all breast cancer cases, whereas EP282 and EPMGHR2 were positive in 37 and 47% of ILC cases, and 49 and 74% of NST cases, respectively. Only data from clones D4D6 and SP384 were highly concordant, while EP282 and EPMGHR2 were positive in distinct breast cancer subtypes.
Conclusions: Assessment of ROS1 status in breast cancer appears to be highly antibody clone-dependent. ROS1 antibody clone selection will be an important consideration in the design of clinical trials investigating the clinical validity of ROS1 as a predictive biomarker in breast cancer.
期刊介绍：
Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.
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