RESUMEN
The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma. Immunohistochemistry of pure DCIS cases constructed in tissue arrays was performed with 16 markers (oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Bcl-2, p53, Her2, insulin-like growth factor receptor, E-cadherin, epithelial membrane antigen (EMA), CA125, keratins 5/6, 14, 19, epidermal growth factor receptor, S100, and CD31). Results in 163 cases were analysed by unsupervised hierarchical clustering. Histological classification was performed by review of whole tissue sections and identified 36 well-, 55 intermediately, and 72 poorly differentiated DCISs. Unsupervised hierarchical cluster analysis categorised DCIS into two major groups that could be further subdivided into subgroups based on the expression of six markers (ER, PR, AR, Bcl-2, p53, and Her2). In the major predominantly ER/Bcl-2-positive (luminal) group, three subgroups (AR-positive (n=33), AR-negative (n=40), and mixed (n=34)) could be identified and included 34 well-differentiated DCISs. Within the major predominantly ER/Bcl-2-negative (nonluminal) group, a Her2-positive subgroup (n=34) was characterised by 31 poorly differentiated lesions. Eight triple-negative lesions, including one positive for keratin 5/6 and two positive for p53, were encountered. Intermediately differentiated DCIS shared a comparable IHC staining pattern with well-differentiated DCIS that was distinct from poorly differentiated DCIS (P<0.001). Ductal carcinoma in situ could be categorised by IHC into two major groups and five subgroups using six markers. Morphologically, intermediately differentiated DCIS seems to have more biological similarities with well-differentiated lesions as compared to poorly differentiated lesions.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Antígeno Ca-125/metabolismo , Cadherinas/metabolismo , Carcinoma Intraductal no Infiltrante/diagnóstico , Femenino , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptor ErbB-2/metabolismo , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: The aim of the study was to assess the risk of invasion and axillary lymph node metastasis in patients with ductal carcinoma in situ (DCIS) diagnosed by preoperative core-needle biopsy. The data were used to select criteria for patients in whom sentinel node (SN) biopsy might be indicated. METHODS: One hundred and seventy-one women with 172 DCIS lesions diagnosed by core-needle biopsy were analysed. Axillary staging was performed by SN biopsy, axillary node sampling, or level 1-2 axillary lymph node dissection. RESULTS: Invasive breast cancer was found in the surgical specimens from 45 tumours (26.2 per cent). Risk factors for invasion were a palpable lesion (odds ratio (OR) 2.95 (95 per cent confidence interval 1.20 to 7.26); P = 0.019), presence of a mass on mammography (OR 3.06 (1.43 to 6.56); P = 0.004), and intermediate (OR 5.81 (1.18 to 28.57); P = 0.030) or poorly differentiated (OR 5.46 (1.17 to 25.64); P = 0.031) tumour grade. Lymph node metastases were found in ten women with DCIS and invasion on final pathology. Factors associated with metastases were age 55 years or less (P = 0.030), invasion of 1.0 cm or more (P < 0.001) and the presence of vascular invasion (P = 0.001). CONCLUSION: SN biopsy should be considered in women with an initial diagnosis of DCIS on core-needle biopsy who are at risk for invasion; this includes women with a palpable lump, a mass on mammography, and intermediate or poor tumour grade.