Typical Medullary Carcinoma Research Articles

Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type.

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 ( P < 0.001), no significant difference in the number of CD4 ( P = 0.154), CD8 ( P = 0.199), and a significantly higher CD8/FoxP3 ratio ( P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage ( P = 0.031), smaller tumor size ( P = 0.010), and negative lymph node status ( P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.

Deep learning based on ultrasound to differentiate pathologically proven atypical and typical medullary thyroid carcinoma from follicular thyroid adenoma

ObjectivesTo investigate the feasibility and value of deep learning based on grayscale ultrasonography in the differentiation of pathologically proven atypical and typical medullary thyroid carcinoma (MTC) from follicular thyroid adenoma (FTA). MethodsThe preoperative 770 ultrasound images consisted of 354 MTCs (66% were typical MTCs with a high suspicion sonographic pattern, 34% were atypical MTCs with a suspicion pattern of intermediate or less) and 416 FTAs. All images were delineated manually by a senior sonographer to achieve the regions of interest. Two deep neural networks of ResNet-34 and ResNet-18 were performed on the training set (n = 690). The test data set (n = 80) was subsequently evaluated by the two models and two sonographers, their diagnostic performances and misdiagnosis lesions were compared and analyzed. ResultsThe ResNet-34 model shows higher diagnostic ability than the junior sonographer with an area under the receiver operating curve of 0.992 (95% CI: 0.840–0.970)versus 0.754 (95% CI:0.645–0.843). Moreover, 12 of 16 atypical MTCs were successfully identified by the ResNet-34, which is significantly better than the senior and junior sonographer, suggesting that these patients could benefit from timely serological examination and surgical strategy at an earlier stage. ConclusionDeep learning to differentiate MTC from FTA on grayscale ultrasound may be a useful diagnostic support tool, especially in atypical MTC and FTA. Moreover, the computing time of deep learning is short, which will help to incorporate it into real-time ultrasound diagnosis.

A Correlation of Pathological Characteristics and Immuno Histo Chemistry (IHC) Based Biomarker Expression in Triple Negative Breast Carcinomas

Background and aim: Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). In India, several reports have suggested that TNBC incidence is higher and up to 31%. Histological features of triple-negative breast cancer are reported to be common with those of basallike subtype, comprising of high-grade invasive ductal carcinoma, no special type, invasive ductal carcinoma with a large central acellular zone, typical medullary carcinoma, and metaplastic carcinomas. In the present study, we aimed to correlate the pathological characteristics and evaluate IHC based expression of basal type biomarkers in triple negative breast carcinomas. Our study showed heterogeneity in histology, most of the TNBC cases in our study were IDC, NOS and there were a slightly higher percentage of atypical medullary cases as compared to other studies. Most of the cases were high grade based on modified NBR grading and majority of them turned out to be basal like on IHC. Distinctly found in our cases which had metastatic axillary lymph node was, basal immune phenotype unlike the case in other studies which demonstrated a higher proportion of lymph node negativity. As expected a high proportion of triple negative tumors showed a consistent basal cytokeratin expression (CK5/6-66%, CK14-72%, CK17-68%). EGFR and p53 positivity did not show statistical significance between basal and non-basal groups. Proliferation marker Ki67 was statistically significant in basal like groups. Gene expression profiling is the gold standard for TNBC molecular subtype classification, however, IHC is an accepted 'surrogate marker' for identifying and classifying the 'basal like group'. Our findings suggest that pathologic characteristics cannot be used to accurately classify triple-negative breast cancer into basal and non-basal groups. Relevance to patients: DNA microarray based molecular profiling may not be accessible always in clinical settings, this study has emphasized that identification of basal like subtype of breast cancers can be done by doing easily available surrogate Immunohistochemical biomarkers on TNBC, and thus help to provide the patient with relevant target based therapeutic benefit.

Carcinoma medular de mama. Caracterización de una serie de casos, 2010-2019

IntroductionMedullary carcinoma of the breast is a rare subtype of invasive carcinoma that accounts for about 3-5% of all cases of breast cancer. The aim of this study was to characterize a series of cases with anatomopathological diagnosis of medullary carcinoma of the mother, from Hospital Clínico Quirúrgico Docente Joaquín Albarrán, in the period 2010 to 2019. MethodA retrospective, descriptive and observational study was conducted, in which the biopsy records were reviewed, collecting variables such as age and macroscopic and histological characteristics. ResultsIn the period from 2010 to 2019, the histopathological diagnosis of 9 cases of medullary carcinoma of the breast was made, of which 77.8% were typical medullary carcinoma of the breast and 22.2%, atypical. Only 33.3% of the lesions presented intratumoral necrosis; lymphatic permeation was present in 100% of cases; lymph node metastasis was confirmed in 33.3% of cases; The immunohistochemical study revealed that 88.9% of the tumors did not express hormonal and Her-2 receptors, so they were classified as triple negative or basal molecular subtype. ConclusionFor the histopathological diagnosis of CMM, the presence of lymphoplasmocytic infiltrate is essential, always detecting the intensity and distribution pattern of lymphocytes and plasma cells in relation to the characteristics of tumor cells (individual disposition and characteristics). The triple negative molecular subtype was the most frequent.

Typical medullary breast carcinoma: clinical outcomes and treatment results

Typical medullary breast carcinoma (T-MBC) accounts for less than 1% of all malignant breast neoplasms, and immu­nohistochemically is characteristic of “triple-negative” breast carcinoma. The purpose of this study was to describe the clinical characteristics and treatment results for patients with T-MBC treated at a single institution, and discuss the controversial aspects of this very rare form of breast cancer. Analyses was performed in 120 patients with T-MBC who were treated between 1970 and 2005. These cases represent 1.1% of all (11 270) patients treated for breast cancer during this period. According to TNM classification, 26 patients (21.6%) were in stage I, 80 patients (66.7%) in stage II and 14 (11.7%) in stage III of clinically advanced breast cancer. Involved axillary lymph nodes occurred in just 10 (8.3%) of the patients, and in all cases metastases were observed in 1–3 lymph nodes. All the patients un­derwent primary surgery. Radical mastectomies were performed on 98 (81.6%) patients, while the other 22 (18.4%) underwent breast-conserving surgery (BCS). Radiotherapy was performed in 36 patients (22 after BCS and 14 after mastectomy). Patients with nodal involvement (10 patients) received adjuvant chemotherapy, and 8 patients with hormone receptor expression received hormonotherapy with tamoxifen. The 10-year DFS rate was 90%. Out of 120 patients with T-MBC, only 4 (3.3%) died from this cancer. We showed that none of the population, neither clinical nor microscopic, had a statistically significant influence on the 10-year disease-free survival rate. Our results are similar to others presented in literature.

Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base.

Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB). Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference. Patients with MBC (n = 3,688), AMCB (n = 288), and IDC (n = 918,870) met inclusion criteria. Comparing MBC with AMCB, the mean age at diagnosis (52.9 vs. 53.9 years), mean tumor size (2.4 vs. 2.5 cm), lymph node positivity (22.8% vs. 22.4%), estrogen receptor (ER) positivity (22% vs. 25%), progesterone receptor (PR) positivity (14% vs. 15%), HER2 positivity (11% vs. 14%), rate of breast conserving surgery (67% vs. 68%), use of chemotherapy (76% vs. 75%), and use of hormonal therapy (19% vs. 18%), respectively, were not clinically or statistically different. Five-year (92% vs. 89%) and 10-year survival rates (85% vs. 87%) were not significantly different (P = 0.46). There does not appear to be any reason to differentiate between AMCB and MBC given the similarities in presentation, treatment and prognosis. J. Surg. Oncol. 2016;114:533-536. © 2016 Wiley Periodicals, Inc.

The Immunophenotype of Nodular Variant of Medullary Carcinoma of the Breast.

The histologic and immunohistochemical profile of typical medullary carcinomas (TMC) of the breast are well established. Among the strict histologic criteria for the diagnosis of TMC is complete circumscription of tumor with pushing borders. Those tumors that do not fulfill all morphologic requirements of TMC are designated as atypical medullary carcinomas (AMC). We herewith describe the histology and immunophenotype of a heretofore undescribed variant of TMC composed of multiple distinctly separate nodules that otherwise meet all other histologic and immunohistochemical phenotypes of TMC. Among 2952 cases of infiltrating mammary carcinomas, 111 (3.8%) met the strict criteria for TMC, including positivity for HLA-DR. Nine of these tumors were composed of multiple separate noncoalescing nodules. Immunohistochemical stains for ER, PR, HER2, and HLA-DR, as well as for p53 and Ki-67 were repeated on these nodular forms. Staining for p63 was used to identify possible intraductal components of these tumors. The age of patients ranged from 34 to 53 years. All 9 patients had negative sentinel lymph nodes. Tumors ranged in the overall size from 2.2 to 3.9 cm and were composed of 3 to 6 distinct nodules ranging in size from 0.2 to 1.1 cm surrounding a larger main tumor nodule. The nodules were composed of syncytial groups of large cells with atypical nuclei and prominent nucleoli. A lymphoplasmacytic infiltrate was present within and around each satellite nodule. Serial sections did not show coalescing of the nodules into a single tumor mass. Similarly, staining for p63 failed to support the possibility of nodules representing intraductal components of main tumor. All tumors were negative for ER, PR, and HER2, but positive for HLA-DR. Eight of 9 tumors were diffusely positive for p53 and all 9 showed a high proliferation index in >70% of tumor cells with Ki-67. We conclude that the nodular variants of medullary carcinomas (nTMC) of the breast are uncommon forms of TMC. They occur in relatively younger women and share the same immunophenotype with TMCs; they are triple negative, express HLA-DR and p53, and show a high proliferative index. As the diagnosis of TMC carries major clinical and prognostic implications, the recognition of its nodular variant becomes equally important.

Clinicopathologic characteristics of typical medullary breast carcinoma: a retrospective study of 117 cases.

PurposeThis study analyzed the clinicopathologic characteristics of typical medullary breast carcinoma (TMBC) in a cohort of Chinese patients.MethodsWe conducted a retrospective review of clinical data including general information, pathologic results, treatment regimens, and patient survival in cases of TMBC diagnosed between February 2004 and April 2011.ResultsA total of 117 patients were enrolled, with a median age of 52 years (range, 28∼92 years). Stage I and II disease accounted for 31.6% and 61.6% of the cases, respectively. Hormonal receptor negative disease (estrogen receptor negative, 68.4%; progestogen receptor negative, 86.3%) was more prevalent in this population. Human epidermal growth factor receptor-2 (HER-2) positivity was 20.5%, while equivocal and HER-2 negative cases represented 16.2% and 63.2% of the cohort. The triple-negative, luminal, and HER-2 overexpressing subtypes constituted 44.4%, 31.6%, and 15.4% of the cases, respectively. The various TMBC subtypes showed no differences regarding tumor size, rates of lymph node(s) metastasis, TNM staging, treatment regimens, and 2-year recurrence rates. However, patients with triple-negative disease were more likely to be younger, when compared to those with luminal disease (P = 0.002). At a median follow-up of 56 months (range, 2–112 months), the 2-year disease-free survival and overall survival rates were 99.1% and 98.2%, respectively.ConclusionEarly stage disease dominated the study cohort, and at two years after surgery, recurrence was extremely low. The heterogeneity of molecular subtypes was clearly shown, and no apparent differences were found among the clinicopathologic characteristics of the triple-negative, luminal, and HER-2 overexpressing subtypes.

CD8+ lymphocytes and apoptosis in typical and atypical medullary carcinomas of the breast

Medullary breast carcinoma (MBC) is a form of ductal invasive carcinoma (DIC) characterized by an abundant infiltration of the tumour by lymphocytes. MBC has been classified histologically into typical medullary carcinoma (TMC) and atypical medullary carcinoma (AMC), with TMC having a better prognosis than AMC and other DIC. The distribution of CD8+ lymphocytes within tumour nests and lymphocyte tracts, and apoptosis in lymphocytes and tumour cells within tumour nests, were studied in archived formalin fixed and paraffin embedded tissues of TMC and AMC. CD8+ lymphocytes tend to accumulate along the margins of lymphocyte tracts that adjoin tumour nests. There were significantly more CD8+ lymphocytes within tumour nests of TMC than AMC. TMC also tended to have more CD8+ lymphocytes within lymphocyte tracts than AMC. Apoptosis of lymphocytes in contact with tumour cells and of tumour cells in contact with lymphocytes was observed in both AMC and TMC within tumour nests but differences in the proportions of apoptotic tumour cells and lymphocytes between the two tumour types could not be established. The findings are consistent with CD8+ cytotoxic lymphocyte-mediated immunity contributing to the more favourable prognosis for TMC compared to AMC.

Protein expression, gene amplification, and mutational analysis of EGFR in triple-negative breast cancer

Although triple-negative breast cancer (TNBC) with epidermal growth factor receptor (EGFR) expression has been extensively studied, few studies have simultaneously examined EGFR expression and EGFR gene amplification. Here, we examined the correlations of EGFR expression with EGFR gene amplification, EGFR-activating mutations, and the expression of components of the Akt pathway. Tumor tissues were obtained from 84 patients with TNBC. We analyzed the expression of EGFR, phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and other relevant proteins using immunohistochemistry. We also analyzed EGFR gene and chromosome 7 copy numbers by dual-color in situ hybridization. DNA was extracted from formalin-fixed paraffin-embedded samples. Analysis of EGFR gene-activating mutations was performed using the smart amplification process version 2 assay. Most TNBCs expressing EGFR are non-specialized invasive ductal carcinomas, whereas others are likely to be rare specialized carcinomas, such as typical medullary carcinoma, apocrine carcinoma, metaplastic carcinoma, and adenoid cystic carcinoma. EGFR was expressed in samples from 28 of 84 (33.3%) patients, but the EGFR gene was not amplified in any of the 84 samples. There were significant correlations between EGFR expression and the number of polysomic cells and the presence of high polysomy of chromosome 7. However, EGFR expression was not correlated with p-Akt or p-mTOR expression, nor with the other clinicopathological factors recorded in this study. We found no evidence of EGFR gene-activating mutations. EGFR gene amplification and EGFR-activating mutations might not be the mechanisms leading to the constitutive activation of EGFR in TNBC. Further investigation is needed to clarify the other molecular mechanisms for oncogenic activation of EGFR in TNBC.

163 Typical medullary carcinoma of the breast: experience of a single institution

163 Typical medullary carcinoma of the breast: experience of a single institution

A study of high-nuclear-grade breast cancer in Thailand: subclassification and correlation with prognostic factors and immunohistochemical study

To classify high-nuclear-grade breast cancer (BC) into typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC), and luminal A, luminal B, and HER2, and to correlate these tumors with other prognostic factors. A retrospective study reviewing high-nuclear-grade BCs. The patients' age, histologic types, various histologic features, axillary lymph node (ALN) status, and results of immunohistochemical (IHC) study were recorded and analyzed. One-hundred and eighty-one cases of high-nuclear-grade BCs were reviewed and categorized into IDC, NOS (140, 77.3%), TMC (1, 0.6%), AMC (21, 11.6%), and others (19, 10.5%). The median age was younger in AMC than in NMC patients. NMC patients had a higher incidence of LVI and ALN metastasis with involvement of more than four lymph nodes (p = 0.006) whereas AMC patients had a higher mitotic index. Forty-six (35.9%) cases were triple-negative (TN), including 1 (100%), 7 (53.9%) and 38 (33.3%) cases of TMC, AMC, and NMC, respectively. AMC had a significantly lower number of node metastases (p = 0.006) than NMC; whereas TN had higher MI (p = 0.001) than non-TN. The non-TN group was subclassified into luminal A, luminal B, and HER2. Of these, TN and luminal B occurred at younger age (p = 0.01) whereas TN and luminal A had a higher mitotic count. TN had lower incidence of LNM including higher number of LNM. Overall, AMC-TN group showed a basal-like prognostic factor expression. NMC may be separated into TN and non-TN, with possibly different behavior. These sub-groupings should continue to be used. Interestingly, luminal A in our study tended to correlate with poor prognostic factors, thus, luminal A with high nuclear grade may not be representative of the usual luminal group profiles.

Clinicopathological characteristics of triple-negative breast cancers

Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors and HER2. Although patients with TNBC tend to have a poor prognosis, only chemotherapy is expected to be effective because no therapeutic targets have yet been established. DNA microarray analyses have proved that TNBCs are composed of the basal-like subtype and normal breast (or unclassified) subtype, the former being correlated with an aggressive clinical course. Histological types of TNBCs are reported to be common with those of basal-like subtype, comprising high-grade invasive ductal carcinoma, no special type [solid-tubular carcinoma (or atypical medullary carcinoma), invasive ductal carcinoma with a large central acellular zone], typical medullary carcinoma, and metaplastic carcinomas. The basal-like subtype is characterized by the expression of myoepithelial/basal markers and molecular changes including TP53 gene mutations, BRCA1 inactivation, and many chromosomal alterations. New target molecules for the treatment of TNBCs are under extensive investigation, and their clinical application is awaited.

Clinical Analysis of Medullary Carcinoma of the Breast

Purpose: Medullary carcinoma of the breast is a variant of breast cancer characterized by the histologic appearance of poorly differentiated cells surrounded by a prominent lymphoid stroma. Medullary carcinoma has been reported to carry a prognosis better than other invasive breast carcinomas, but it is frequently overdiagnosed due to the difficulty in diagnosis. The aim of this study was to assess the clinical manifestations and outcome of medullary carcinoma of the breast. Methods: We reviewed the data of 91 patients diagnosed with medullary carcinoma and 3,743 patients with invasive ductal carcinoma, not otherwise specified (NOS) from January 1980 to December 2005 at Yonsei University Severance Hospital. The clinicopathologic features, disease free survival (DFS) and overall survival (OS) for patients with medullary carcinoma were compared with those of the NOS patients. Results: With reviewing the pathologic slides, 69 (75.8%) patients had findings compatible with typical medullary carcinoma (TMC) and the remaining 22 (24.2%) patients were reclassified as atypical medullary carcinoma (AMC). Early stage cancer was more frequent at medullary carcinoma and lymph node positive cancer was less frequent at medullary carcinoma. The expression of ER/PR was positive in either the TMC (18.9%/16.2%) and AMC (15.0%/20.0%) as compared to the NOS (63.2%/57.2%), and the difference was significant (p<0.001). In contrast, the HER-2/neu expression rate was significantly higher in the TMC (47.4%) and AMC (45.5%) than in the NOS (28.3%, p=0.001). The 10year disease free survival and 10-year overall survival of the atypical medullary carcinoma patients (67.8%, 77.8%) were in fact similar to the NOS carcinoma patients (68.3%, 74.7%). There was significant difference in 10-year disease free survival and 10-year overall survival between the TMC (77.8%, 86.0%) and NOS carcinoma (68.3%, 74.7%) patients (p=0.002, p=0.006). Conclusion: The clinical outcome of typical medullary carcinoma is favorable in spite of its aggressive pathologic features and it differs from atypical medullary carcinoma. For precise prediction of prognosis of medullary cancer, we should apply strict criteria for the diagnosis of subtype with medullary features.

Carcinoma medular da mama: correlação anátomo-radiológica

OBJETIVO: Avaliar as características radiológicas do câncer de mama medular em pacientes submetidas a tratamento cirúrgico no Instituto Nacional de Câncer (INCA) - Ministério da Saúde, Rio de Janeiro, RJ, correlacionando os achados com estudo histopatológico. MATERIAIS E MÉTODOS: Foi realizado estudo descritivo retrospectivo de mulheres submetidas a tratamento cirúrgico no INCA, no período de janeiro de 1997 a dezembro de 2006, para identificação das pacientes com carcinoma medular e análise dos achados radiológicos. RESULTADOS: Foram identificadas 21.287 pacientes com diagnóstico de carcinoma neste período, sendo 76 pacientes com diagnóstico de carcinoma medular típico (0,357%). Nessas pacientes selecionadas, a idade média foi de 51,9 anos (32 a 81 anos). Dezenove pacientes apresentavam lesão na mamografia, sendo 17 (89,5%) nódulos e 2 assimetrias focais (10,5%). Entre as pacientes com nódulo, 15 (88,1%) apresentavam alta densidade e 2 eram isodensos (11,9%). Doze pacientes apresentavam achados ultra-sonográficos e, destas, 11 (91,6%) apresentavam nódulos hipoecóicos. Foi observada uma paciente com nódulo anecóico com áreas de degeneração cística. CONCLUSÃO: O nódulo foi o achado radiológico dominante (89,5%), dos quais 88,1% apresentaram nódulos com alta densidade e margens circunscritas. Apesar das características radiológicas de benignidade, um nódulo com alta densidade, sólido, margens circunscritas e crescimento rápido deve ser investigado para confirmar o diagnóstico.

Carcinome médullaire typique du sein : étude rétrospective à propos de 33 cas

Objective Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. It represents less than 5% of all breast cancer. It is known for its favourable prognosis. Considering the rarity of the series we could retrieve, we aimed at underlining the particularities of this pathology. Patients and methods Retrospective study about 33 cases of typical medullary carcinoma managed at the Salah-Azaïz Institute during a period of six years between 1994 and 1999. Results The mean age was 47.5 years. The left breast was concerned in about 55% of cases. Mean tumoral size was 46 mm. Sixty-one percent of our patients were treated by radical surgery. Seventy-three percent undergo radiotherapy, 57% chemotherapy and 42% hormonotherapy. The five-year free-disease survival was about 85%. Discussion and conclusion Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. Its treatment is similar to the other breast cancers. Our results agree with the different published studies and confirm its favourable prognosis.

Mismatch Repair Genes hMLH1 and hMSH2 May Not Play an Essential Role in Breast Carcinogenesis

Breast carcinoma is one of the most common malignancies in women, and its carcinogenesis is still unknown. The role of microsatellite instability (MSI) in breast carcinogenesis has been inconsistent in the literature. Here we studied the expression of 2 mismatch repair genes, hMLH1 and hMSH2, in 211 cases of intraductal (DCIS; 90 cases) and invasive ductal carcinoma (121 cases) of the breast by immunohistochemical analysis; and evaluated its relationship with cytokeratin (CK) subtypes, along with expression of ER-alpha (138 cases positive, 73 cases negative); PR (118 cases positive, 93 cases negative), and HER-2/neu (47 cases positive, 164 cases negative); and clinical features such as patient age (157 cases>50 years, 54 cases<50 years), tumor size (31 cases of IDC>2 cm, 90 cases of IDC<2 cm), tumor grade (87 cases high nuclear grade, 124 case non-high grade), and lymph node metastasis (38 cases of IDC positive, 74 cases of IDC negative, 9 cases of IDC with no available data on lymph node status). For CK subtypes, 167 cases were classified as luminal subtype (expressing CK8 and/or CK18, negative for CK5/6, CK14, and CK17) and 44 cases were classified as nonluminal (most of them belonged to basal/stem subtype, expressing CK5/6, and/or CK14, and/or CK17). No typical or atypical medullary carcinoma was included in this study. Our results showed that no loss of nuclear expression of either hMLH1 or hMSH2 was identified in any of the 211 cases of DCIS or IDC regardless of the various pathological and clinical factors, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.

Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity

IntroductionTypical medullary breast carcinoma (MBC) has recently been recognized to be part of the basal-like carcinoma spectrum, a feature in agreement with the high rate of TP53 mutations previously reported in MBCs. The present study was therefore designed to identify phenotypic and genetic alterations that distinguish MBCs from basal-like carcinomas (BLC).MethodsExpression levels of estrogen receptor (ER), progesterone receptor (PR), ERBB2, TP53, cytokeratins (KRTs) 5/6, 14, 8/18, epidermal growth factor receptor and KIT, as well as TP53 gene sequence and high-density array comparative genomic hybridization (CGH) profiles, were assessed and compared in a series of 33 MBCs and 26 BLCs.ResultsAll tumors were negative for ER, PR and ERBB2. KRTs 5/6 were more frequently expressed in MBCs (94%) than in BLCs (56%) (p = 0.0004). TP53 mutations were disclosed in 20/26 MBCs (77%) and 20/24 BLCs (83%). Array CGH analysis showed that a higher number of gains (95 regions) and losses (34 regions) was observed in MBCs than in BLCs (36 regions of gain; 13 regions of losses). In addition, gains of 1q and 8q, and losses of X were found to be common to the two groups, whereas gains of 10p (53% of the cases), 9p (30.8% of the cases) and 16q (25.8% of the cases), and losses of 4p (34.8% of the cases), and amplicons of 1q, 8p, 10p and 12p were the genetic alterations found to characterize MBC.ConclusionOur study has revealed that MBCs are part of the basal-like group and share common genomic alterations with BLCs, the most frequent being 1q and 8q gains and X losses; however, MBCs are a distinct entity within the basal-like spectrum, characterized by a higher rate of KRT 5/6 expression, a higher rate of gains and losses than BLCs, recurrent 10p, 9p and 16q gains, 4p losses, and 1q, 8p, 10p and 12p amplicons. Our results thus contribute to a better understanding of the heterogeneity in basal-like breast tumors and provide potential diagnostic tools.

Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n=44) and non-TMBC grade III with no or low scores (n=160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n=17) and non-MBC grade III cases (n=140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45).