Subtype Of Invasive Breast Carcinoma Research Articles

Bilateral Pleomorphic Ductal Carcinoma Of Breast- A Rare Presentation With Its Diagnostic Dilemma

Pleomorphic carcinoma of breast is a rare morphological subtype of Invasive Breast Carcinoma No Special Type (IBC NST), which has histomorphological overlap with other entities. Here we present such a case with bilateral breast involvement in 45 years old nulliparous woman with family history of breast carcinoma. Typical numerous multinucleated cells (>50%) with marked pleomorphism and wide areas of necrosis were histopathological presentation. AE1/AE3 and Vimentin were positive. Ki-67 labelling index was high along with HER2 amplification. Important differentials were IBC NST with Osteoclast-like giant cells, Choriocarcinomatous pattern, metaplastic carcinoma & metastatic disease all of which was ruled out with proper clinical, histological & immunohistochemical approach. Despite the aggressive nature of the neoplasm and presence of adverse prognostic factors, this case responded well with adjuvant chemotherapeutic regimen.International Journal of Human and Health Sciences Vol. 06 No. 02 April’22 Page: 213-216

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study.

Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups - Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Chi-square test, univariate and multivariate logistic regression models were used. Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades. TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Association between Molecular Subtype of Invasive Breast Carcinoma with grade, lymphovascular invasion and lymph node metastasis in the Department of Anatomic Pathology FKUI/RSCM 2019

BackgroundBreast cancer is classified into molecular subtypes: luminal A, luminal B, HER2 enriched and triple negative breast cancer based onits immunohistochemical profile. This study aims to assess the relationship between histologic grade, lymphovascular invasion andlymph node metastasis with molecular subtypes in invasive breast carcinoma at Cipto Mangunkusumo Hospital from January 1,2019 to December 31, 2019.MethodsA descriptive, cross-sectional study was conducted in Anatomical Pathology Department, FKUI/RSCM over a period of January toDecember 2019. A total of 652 histologic specimens with a diagnosis of invasive breast carcinoma which were immunostained withER, PR, HER2, and Ki67 were reviewed, then grouped into the appropriate molecular subtypes. A Chi-square test was performed toassess the association between histologic grade, lymphovascular invasion and regional lymph node metastases with molecularsubtypes.The p-value <0.05 was statistically significant.ResultsThe molecular subtypes of breast cancer, from the highest to the least number, were luminal A (40.2%), luminal B (37.7%), TNBC(13.6%), and HER2 enriched (8.6%). There was a significant association between grade and molecular subtypes of breast cancer.(p=<0.001). There was a significant association between lymph node metastasis and molecular subtypes of breast cancer(p=0.038).ConclusionThe most common molecular subtype of invasive breast cancer found was Luminal A. There was a significant association betweenlymph node grade and metastasis and the molecular subtype of breast cancer.

Molecular Subtyping of Invasive Breast Carcinoma by Immunohistochemistry and Five-Year Survival Study

Background: Global gene expression profiling for Invasive breast carcinoma (IBC) has identified intrinsic subtypes of IBC with differing clinical outcomes and response to therapy. As genotyping assays are limited by availability and cost, we have used Immunohistochemistry (IHC) surrogates to classify IBC into molecular subtypes.
 Methods: Representative tumor blocks of 158 surgical specimens of IBC between 2007 to 2017, were selected and IHC done for ER, PR, Her2, Ki67, CK 5/6 and EGFR. The cases were classified into 7 Molecular subtypes (Luminal A, Luminal B, Luminal HER2PR+, Luminal HER2PR-, HER2Enriched, Basal like (BLBC) and non classifiable (NCBC) and correlated with clinico-pathological findings. Five- year survival rate was calculated for patients diagnosed between 2007 to 2013.
 Result: The most common subtype was Luminal A (31.0%), followed by Luminal B (25.3%), NCBC (14.6%) and HER2 enriched (13.3%). Among post-menopausal women, common subtypes were Luminal A (33.8%) and Luminal B (24.4%). Among premenopausal women, most cases were NCBC (27.8%) and BLBC (22.2%). 61.2% of Luminal A were Grade2 and 22.4% were Grade 1. Many cases of Luminal B and HER2 positive cases were of Grade3 (45.0%) and (57.1%) respectively. Of the triple-negative category (BLBC & NCBC), 73% were Grade3 with statistically significant correlation (p value < 0.001). Most of these cases were in Tumor stage T2 (70%), followed by T1 (22.3%). Nodal metastasis was seen in 39.6% and 65% respectively of Luminal A and Luminal B subtypes. Distant metastases on follow-up were present in 15.8%, which included HER2 enriched subtype (28.5%), followed by BLBC (20.0%) and NCBC (17.4%). Luminal A cases, had better survival accounting for 88% of all survivors.
 Conclusion: Molecular subtyping of IBC using IHC was useful to understand the clinicopathological distinctiveness of each subtype.

Tall cell carcinoma with reversed polarity – a case report

Tall cell carcinoma with reversed polarity is a rare subtype of invasive breast carcinoma. Immunohistochemical and molecular research show that it is a distinct entity. It is negative for thyroid specific markers.1 It also has its own unique molecular mutations (IDH2 hotspot mutations and PI3K pathway mutations).2 We present a case of tall cell carcinoma with reversed polarity in the breast of an 81-year-old woman. The lesion showed papillary morphology and columnar cells exhibiting reversed nuclear polarity. Immunohistochemistry showed the tumour cells were positive for CK5/6. They showed weak positivity for GATA3 and GCDFP and were negative for TTF-1. Stains for p63 and p40 showed an absence of myoepithelial cells around tumour nests. The core biopsy showed triple negative hormone receptor status. Further molecular testing was performed which showed a mutation in the PIK3CA gene. An activating mutation in the IDH2 gene was also detected. The combination of morphologic, immunohistochemical and molecular findings are diagnostic of tall cell carcinoma with reverse polarity. It can present a diagnostic challenge when encountered. IDH2 and PI3K mutation testing may provide more confidence with diagnosing these lesions and to help distinguish it from other breast neoplasms. 1.WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Breast Tumours. 5th ed. Lyon: IARC, 2019.2.Zhong E, Scognamiglio T, D'Alfonso T, et al. Breast tumour resembling the tall cell variant of papillary thyroid carcinoma: molecular characterization by next-generation sequencing and histopathological comparison with tall cell papillary carcinoma of thyroid. Int J Surg Pathol 2019; 27: 134–41.

Molecular profiling of breast carcinoma with IHC surrogates in a tertiary care centre in South India

Introduction and Aim: Breast cancer is the most common malignancy in females worldwide. Almost 1.4 million new cases have been diagnosed with breast cancer every year. This aims to study the clinicopathological profile and molecular subtypes of invasive breast carcinoma in resected mastectomy specimens over a period of 5 years.
 Materials and Methods:A retrospective study of 90 mastectomy and wide local resection specimens received during the period of January 2012 to June 2017 were analyzed. The clinical data of patients including age, gender, and stage of the diseasewere obtained from the medical records section. Immunohistochemical staining for Estrogen Receptor [ER], Progesterone Receptor[PR] and Human Epidermal Growth Factor Receptor 2HER2neu were done.The cases were classified according to the molecular classification based on the ER, PR and HER2 receptor status.
 Results: The peak incidence of breast carcinoma was in the age group 50 to 60 years. Invasive ductal carcinoma,Not otherwise specified[NOS] accounted for the most common histologic type. There was higher incidence of pT2 tumors in our study. The most common molecular subtype was luminal A, followed by triple negative tumors. These molecular subtypes associated well with Tumor grade and HGDCIS with a statistically significant p value of 0.001 and 0.015 respectively. An increased proportion of Grade 3 tumors were Triple Negative tumors.
 Conclusion:In breast carcinomas the routine histopathological features provide inexpensive method for understanding tumour biology and prognosis. It`s essential in areas with poor resources. ER, PR and HER2 assessment helps in identifying hormonal status and enables for hormone therapy and anti HER2 therapy.

Glycogen-rich clear cell carcinoma of the breast with solid papillary pattern: Two cases with heterogeneous clinicopathological features.

Invasive breast cancer is a heterogeneous disease, both in its histopathological classification and clinical course. Glycogen-rich clear cell carcinoma of the breast is an extremely rare subtype of invasive breast carcinoma, accounting for up to 3% of all breast carcinomas. The tumor is composed of polygonal cells with abundant clear cytoplasm containing glycogen and has a very controversial prognosis. Solid papillary pattern is an uncommon morphological variant of breast carcinoma which is associated with indolent behavior in the absence of an invasive component. To date, there are only three cases of glycogen-rich clear cell carcinoma with solid papillary pattern reported in the English literature. In this article, we present two cases of glycogen-rich clear cell carcinoma of the breast, encountered in our daily clinical practice over a period of 5 years (2015-2020) and perform a brief review of currently published literature. Unlike most cases of glycogen-rich clear cell carcinoma documented to date, follow-up of our case featuring solid papillary pattern revealed extremely favorable clinical outcome, suggesting a better prognosis for tumors with this morphology.

Prognostic significance of tumour infiltrating lymphocytes in different molecular subtypes of invasive breast carcinoma

Metastasis is the main cause of death from cancer, including breast cancer, so the search for simple and effective prognostic parameters is becoming a priority for researchers. The number of tumor-infiltrating lymphocytes is a proven prognostic factor for triple negative and Her2-positive, but not luminal, molecular subtypes of breast cancer. Possible reasons for the failure of this prognostic parameter for luminal subtypes of breast cancer may be the tumor morphological heterogeneity. Objective: to assess the prognostic significance of the tumor-infiltrating lymphocytes number in the invasive breast carcinoma of a non-specific type (IC NST) of various molecular subtypes, taking into account its morphological heterogeneity. 152 patients with IC NST (T1-3N0-2M0) aged 29 to 75 years were enrolled in the study. The molecular subtype was determined using immunohistochemical analysis of the expression of estrogen and progesterone receptors, Ki-67 and Her2/neu. TILs were assessed in accordance with the recommendations of the International TILs Working Group. It was shown that TILs near the structures of various types is heterogeneous only in patients with the luminal Her2-negative subtype of IC NST. In addition, was found that the development of hematogenous metastases and worse metastatic-free survival in this cohort of patients is associated with a high TILs near solid structures and also depended on Ki-67 level. Thus, TILs near solid structures is a potential prognostic factor for the development of distant metastasis in the luminal Her2-negative and Ki-67 level less 20% subtype of IC NST.

Prognostic relevance of the loss of stromal CD34 positive fibroblasts in invasive lobular carcinoma of the breast

CD34+ fibroblasts are constitutive stromal components of virtually all organs, including the mammary stroma, being involved in matrix synthesis, antigen presentation, and tumor-associated stromal remodeling. The most common subtype of invasive breast carcinoma, invasive carcinoma of no special type (IBC-NST), is known for its stromal loss of CD34+ fibroblasts while acquiring alpha smooth muscle actin-positive (α-SMA+) myofibroblasts, i.e., cancer-associated fibroblasts (CAF), whereas invasive lobular carcinoma (ILC) displays partial preservation of CD34+ fibroblasts. The aim of this study was to evaluate the prognostic relevance of stromal CD34+ fibroblasts and α-SMA+ myofibroblasts in an extended collection of ILC. A total of 133 cases of ILC, primarily resected between 1996 and 2004 at University Hospital Marburg, were examined semiquantitatively for stromal content of CD34+ fibroblasts and α-SMA+ myofibroblasts. Partial preservation of CD34+ fibroblasts in the tumor stroma of ILC was confirmed. Absence of CD34+ fibroblasts in the tumor stroma significantly correlated with the presence of α-SMA+ myofibroblasts (p = 0.010), positive lymph node status (p = 0.004), and pN stage (p = 0.006). Stromal loss of CD34+ fibroblasts was significantly associated with lower overall and disease-free survival rates (p = 0.012 and 0.013, respectively). Multivariate analysis adjusted for pT and pN stage revealed stromal loss of CD34+ fibroblasts as independent prognostic parameter (p = 0.05). To our knowledge, this is the first report defining prognostically relevant stromal subtypes of ILC with long-term follow-up. Future research targeting the potential diagnostic and therapeutic implications of CD34+ fibroblasts and CAF in breast cancer, especially ILC, is a promising field of interest.

Report of Two Cases with Simultaneously Detected Tubular Carcinoma and Phyllodes Tumor of the Breast

Tubular carcinoma (TC) is a subtype of invasive breast carcinoma with better prognosis, and phyllodes tumors (PT) are rare fibroepithelial lesions. Accurate preoperative pathological diagnosis allows for correct surgical planning and avoidance of reoperation for these breast neoplasms. A database was created by analyzing the archives of Department of General Surgery of the İstanbul Faculty of Medicine between September 2006 and November 2017, and a total of 105 PTs and 55 TCs were collected. Two cases with concurrence of TC and PT were identified and examined in detail. The first patient was a 33-year-old woman with a 20×12 mm2 TC and a 65×32 mm2 malignant PT in the left breast. The second patient was a 28-year-old woman with two masses in the right breast. The first mass was 38×16 mm2 on the upper outer quadrant, and the second mass was 10×8 mm2 in size in the lower inner quadrant, accompanied by a 16×10 mm2 TC and a 33×26 mm2 borderline PT. Both cases were treated by mastectomies due to patient's decisions or insufficient margin control. This study extrapolated that if two tumors are detected simultaneously, margin control can become more difficult, and breast-conserving surgery should be thoroughly reviewed.

Correlation of Apparent Diffusion Coefficient Value Factor with Different Molecular Subtypes of Invasive Breast Carcinoma

Correlation of Apparent Diffusion Coefficient Value Factor with Different Molecular Subtypes of Invasive Breast Carcinoma

Secretory breast carcinoma in adulthood: A case report with literature review

Introduction. Secretory breast carcinoma is rare subtype of breast carcinoma which occurs primarily in children and young adults, so in the past it was called juvenile carcinoma. Case report. A 67-year-old female patient presented with mass of the right breast since one month. After physical, routine laboratory examination and mammography, core needle biopsy was performed and histopathological examination confirmed invasive carcinoma. Immunohistochemically, estrogen-receptors (ER) and progesteron-receptors (PR) showed weak positive reaction in 10% of tumor cells, while human epidermal growth factor receptor-2 (HER-2) was without expression. After an adequate preoperative preparation, operation was done ? quadrantectomy with sentinel lymph node biopsy. Postoperatively, the patient was treated with 6 cycles of cyclophosphamide, methotrexate and fluorouracil (CMF) combination, radiotherapy (60 Gy) and tamoxifen. After 5-year follow-up the patient had no signs of the disease. Conclusion. Secretory breast cancer is a rare subtype of invasive breast carcinoma with wide age range of occurrence and good prognosis despite its triplenegative immunophenotype. Although the therapeutic management is non-consensual for this breast cancer special type, surgery is considered the mainstay of the treatment as well as the adjuvant chemotherapy and radiation.

Surrogate Molecular Classification of Invasive Breast Carcinoma: A Comparison Between Core Needle Biopsy and Surgical Excision, With and Without Neoadjuvant Therapy.

Surrogate molecular classification identifies different subtypes of invasive breast carcinoma on the basis of their immunohistochemical markers. The purpose of the study is to verify whether the immunohistochemical markers and surrogate molecular subtypes can be correctly assessed on the core needle biopsy (CNB) when compared with the corresponding surgical excision (SE), with or without neoadjuvant treatment (NAT). Cases with invasive carcinomas identified on both CNB and SE were retrospectively selected. With immunohistochemistry for estrogen receptors (ER), progesterone receptors (PgR), Ki67, human epidermal growth factor receptor 2 (Her2), and molecular analysis for Her2, surrogate molecular classification was determined in 4 and 5 groups, according to the 2013 St Gallen consensus. A total of 1067 cases was considered and complete data for surrogate molecular classification were available for 988 cases (655 without NAT, 333 with NAT). Without NAT, concordance was strong for ER and Her2, moderate for PgR, and weak for Ki67; concordance for surrogate molecular classification was moderate. After NAT, lower concordance rates were recorded, with significant reduction of PgR (P<0.001) and Ki67 (P<0.001). Without NAT, the surrogate molecular subtypes of breast carcinoma can be reliably assessed on CNB; Ki67 and/or PgR may be repeated on SE when values are close to cutoffs to avoid tumor subtype misclassification. After NAT, it seems advisable to repeat at least Ki67 and PgR.

Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma.

Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer. We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups. TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance. Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.

Breast cancer histologic subtypes show excess familial clustering.

The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype. By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives. The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n=178], lobular [n=1688], and mucinous [n=542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P=.011) as well as for inflammatory breast cancers (P=.024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P=.03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P<.001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P=.00021) subtypes. These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.

Mixed invasive ductal-lobular carcinoma: Clinicopathological characterization and clinical outcomes.

e12531 Background: Mixed Invasive Ductal-Lobular Carcinoma (IDC-L) is a histological subtype of invasive breast carcinoma comprised of both ductal and lobular morphologies. There is limited information on the relative proportions of the individual components in IDC-L and on outcomes compared to invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Methods: Clinical information was abstracted from 16,308 patients with invasive breast cancer seen at UPMC Magee Women’s Hospital from 1990-2017 using the UPMC Network Cancer Registry. A systematic chart review was performed on a subset of patients annotated with IDC-L (n=806); however, a thorough review of pathology reports led to the exclusion of all but 408 patients for further analysis, due to the lack of a standardized definition of IDC-L. Of the 408 cases, 92% were estrogen receptor (ER)+. Survival of patients with ER+ IDC-L (n=376) was compared to ER+ IDC (n=9,716) and ER+ ILC (1,465). For a subset of IDC-L cases (n=54), distributions of individual subtype components were abstracted from pathology reports. Results: IDC-L made up 2.5% of the total cases (408/16,308). IDC-L tumors were on average 31% ductal and 69% lobular (p =0.001). Survival analysis showed worse disease free survival (DFS) (p=0.05) and overall survival (OS) (p=0.002) in patients with ER+ ILC compared to ER+ IDC, with ER+ IDC-L patients showing a median OS superior to ILC yet inferior to IDC counterparts (ns). Conclusions: Identification of patients with IDC-L through cancer registry protocols representative of standard practices by national cancer registries revealed a lack of a standardized definition of mixed IDC-L. Reliance on accuracy of these diagnoses calls in to question the reliability of prior clinico-pathologic analyses reported on this topic. DFS and OS of IDC-L patients falls between that of IDC and ILC patients while ILC patients showed significantly worse outcome. The predominant distribution of lobular morphology in IDC-L tumors suggests this subtype may have additional characteristics similar to lobular rather than ductal carcinomas. Comprehensive clinical and molecular characterization of a carefully identified IDC-L cohort is underway.

PO-231 CTXIII expression around single tumour cells of invasive breast carcinoma

Introduction Studies of breast carcinoma indicated the presence of type I and III collagens localization at the invasion front of the tumour. Mesenchymal invasion accompanied by proteolysis, in particular collagens, and remodelling of tissue structures by matrix metalloprotases. Possible marker of this process is expression of Cross Linked C-telopeptide of Type III Collagen (CTX-III). The project is aimed to study frequency of CTX-III expression around different of single tumour cells subtypes of invasive breast carcinoma of no specific type. Material and methods Fourteen patients with invasive breast carcinoma of no specific type (IC NST, all molecular subtypes, T1-3N0-3M0) were enrolled in study. CTX-III expression around different subtypes of single tumour cells were analysed in FFPE tumour samples using confocal microscope LSM780 (Carl Zeiss, Germany). Results and discussions CTX-III expression around single tumour cells was observed at 21% of breast cancer patients. In positive cases only 5% of single tumour cells were express CTX-III and these cells have features of stemness, EMT or both. Conclusion Only small part of single tumour cells showed signs of a mesenchymal type of invasion, and it didn’t depend on the state of stem and EMT. The study was supported by RSF (#16-15-10221).

Diagnostic significance of intratumoral CD8+ tumor-infiltrating lymphocytes in medullary carcinoma

Invasive ductal carcinomas of breast with marked stromal lymphocytic infiltration have come to be classified as lymphocyte-predominant breast cancer (LPBC) because it obtains high pathological complete response rates with neoadjuvant chemotherapy. Medullary carcinoma (MC), which is independent from LPBC, is a rare histological subtype of invasive breast carcinoma accompanied by abundant lymphoplasmacytic infiltration as LPBC. Although MC shows marked cellular and structural atypia, it usually has a favorable outcome. It is occasionally difficult to distinguish MC from LPBC because both subtypes have nonspecific morphological features according to the present diagnostic criteria. Herein, we adopted multiplexed fluorescent immunohistochemistry to perform quantitative and simultaneous analyses of tumor-infiltrating lymphocytes (TILs) considering their spatial distribution and examined focal immune reaction differences between MC and LPBC. We found that CD8+ TILs are predominant in the intratumoral region, whereas CD4+ TILs are less common in MC. In non-luminal-type cancers, the numbers of stromal and intratumoral CD8+ TILs were significantly higher in MC than in LPBC. Stratified analyses by CD4+ TIL subsets showed robust infiltration of intratumoral CD8+ TILs in non-luminal-type MC even in suppressive environments, such a low T helper 1-to-regulatory T cell ratio. Our results suggest that extensive intratumoral CD8+ TIL infiltration might well be a promising biomarker for distinguishing MC from LPBC, especially in non-luminal-type cancers. Intratumoral CD8+ TILs and nonluminal intrinsic subtypes may serve as diagnostic characteristics allowing reliable histological criteria to be established for reproducibly diagnosing MC.

Immunohistochemical characterization of the molecular subtypes of invasive breast carcinoma in a series of Egyptian female patients with clinicopathologic correlation

Immunohistochemical characterization of the molecular subtypes of invasive breast carcinoma in a series of Egyptian female patients with clinicopathologic correlation

Abstract 5802: Role of mesenchymal stem cells in acquisition of metaplasia in AKU-BC42 breast metaplastic carcinoma cell line

Abstract Introduction: Metaplastic carcinoma (MCa) is a rare and aggressive subtype of invasive breast carcinoma exhibiting epithelial to mesenchymal transition (EMT) where tumor of epithelial origin manifests differentiation into non-glandular, mesenchymal phenotypes such as spindloid, chondroid or osseous components. Acquisition of EMT is associated with low expression of e-cadherin, claudins and high expression of vimentin. Biological mechanisms for acquisition of metaplastic components within MCa are not well understood. The present study was undertaken to establish and characterize a cell line from a patient diagnosed with MCa and to evaluate the role of mesenchymal stem cells (MSC) in attainment of metaplastic phenotype. Methodology: AKU-BC-42 was established from a 65 years old Pakistani female patient diagnosed with T4N1M0 MCa. Specimen was procured and processed under sterile conditions and cultured in DMEM supplemented with 10% FBS. Epitheloid colonies were visualized after 3 weeks of culture, which were passaged and propagated. AKU-BC-42 was phenotypically and genotypically characterized using karyotyping, gene expression analysis, immunocytochemistry and florescent insitu hybridization. MSC marker expression was assessed by flow-cytometry. AKU-BC-42 was cultured under appropriate conditions for assessment of differentiation along osteogenic, adipogenic and chondrogenic pathways. Lineage differentiation was evaluated by special immunohistochemical stains and induction of lineage differentiation genes was assessed by Q-PCR. Results: AKU-BC-42 was found to have a human karyotype with multiploidy and population doubling time of 60 hours. Gene expression profiling revealed negative expression for estrogen and progesterone receptors and positive expression of androgen receptor (AR) and HER-2/neu. FISH analysis was negative for HER-2/neu amplification. Basal (5, 14 &amp; 19) and luminal cytokeratins (8 &amp; 18) were expressed at mRNA level along with myoepithelial markers (CD10, S100A7, p-cadherin, desmin, S100A4, S100A2 &amp; á-SMA). AKU-BC-42 demonstrated MSC pool with expression of CD73 (79.2%), CD90 (10.3%) and CD105 (30.2%) as revealed by flow-cytometry. Osteogenic differentiation was assessed by von kossa stain for mineralization with up-regulation of ALPL and OPN genes. Similarly, differentiation of AKU-BC-42 into mature adipocytes was evaluated with Oil red O staining of lipid droplets and expression of FABP4 gene. Chondrogenic induction was achieved by performing pellet cultures. Collagen synthesis in extracellular matrix of chondrogenic beads was assessed by mason trichrome staining with up-regulation of ACAN, COL10A1 and COMP. Conclusions: We report a novel MCa cell line containing a MSC pool. MSC pool within MCa may be responsible for acquisition of metaplasia in this rare subtype of breast cancer. Further studies on this cell line may reveal the biological mechanisms of MCa of the breast. Citation Format: Nazia Riaz, Sadia Habib, Azhar Hussain, El-Nasir Lalani. Role of mesenchymal stem cells in acquisition of metaplasia in AKU-BC42 breast metaplastic carcinoma cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5802. doi:10.1158/1538-7445.AM2017-5802