Abstract S6-9: Expression of Hedgehog Proteins in the Epithelial and Stromal Compartments of Primary Breast Tumors and Its Prognostic Significance

Abstract Background: Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited. Methods: This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival. Results: CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P=0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2 % of Grade 1 cases were GATA3 negative (P<0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor. Conclusions: This is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.

Download Full-text

Use of multiplex mutation genotyping to identify novel and protective mutations in breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.11004 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 11004-11004

Author(s):

K. Kalinsky ◽

L. M. Jacks ◽

C. Hedvat ◽

U. Bhanot ◽

S. Patil ◽

...

Keyword(s):

Breast Cancer ◽

Pik3ca Mutation ◽

Prognostic Significance ◽

Predictive Biomarkers ◽

Breast Tumors ◽

Tumor Biomarker ◽

Lower Grade ◽

Cancer Specific Survival ◽

Mutation Status ◽

Pik3ca Mutations

11004 Background: We recently analyzed 590 primary invasive breast tumors for PIK3CA mutations by multiplex massARRAY genotyping. We identified a 32.5% PIK3CA mutation rate (manuscript submitted). Associations between PIK3CA mutation status and favorable pathology, such as lower grade tumors, lymph node negativity and hormone receptor (HR) positivity, were observed. Multiplex analysis allows the rapid assessment of mutations not commonly described in breast cancer. To identify activated pathways that may serve as predictive biomarkers, tissue microarrays (TMA) underwent immunohistochemical (IHC) analysis. Methods: 590 archival formalin-fixed paraffin embedded (FFPE) tumors > 1 cm were used to ensure adequate tissue procurement for mutation detection and TMA construction. MassARRAY (Sequenom) genotyping was performed on native DNA to identify PIK3CA, RAS, RET, and other known mutations. IHC staining of the TMAs included assessment of steroid nuclear receptors, HER2 expression, Akt pathway activation (including pAKT, p70S6K, eIF4E), and PTEN. Stained TMAs underwent digital quantitative image analysis and scoring (Aperio, Vista, CA). The Kaplan-Meier method and Cox models were used in univariate and multivariate analysis for associations of mutation status and clinicopathologic features on overall survival (OS) and breast cancer-specific survival (BCSS). Results: Compared to wild-type, PIK3CA mutated tumors (median f/u: 12.8 years) demonstrate a significant improvement in OS (p=0.03) and BCSS (p=0.004). For patients with any PIK3CA mutation, the improvement in BCSS is maintained in HR positive and ER negative subgroups. In addition to PIK3CA mutations, RAS and RET mutations are identified in a small proportion of breast tumors. Additional analysis to evaluate the association of mutation status and biomarker data derived from the TMA analysis will be performed for meeting presentation. Conclusions: We have recently defined the positive prognostic significance of PIK3CA mutations in breast cancer. RAS mutations are confirmed to occur rarely in breast cancer. The finding of RET mutations in breast cancer is novel. Future tumor biomarker identification directed towards predictive measurement will assist in tailoring therapy to appropriate patient populations. No significant financial relationships to disclose.

Download Full-text

Cell cannibalism: a diagnostic and prognostic marker of breast cancer

International Surgery Journal ◽

10.18203/2349-2902.isj20201396 ◽

2020 ◽

Vol 7 (4) ◽

pp. 1195

Author(s):

Mir Mohsin ◽

Haroon Rashid Zargar ◽

Mohammad Amanullah Khan ◽

Rana Sherwani

Keyword(s):

Breast Cancer ◽

Tumor Cell ◽

Tumor Cells ◽

Histopathological Examination ◽

Prognostic Significance ◽

Metastatic Breast ◽

Breast Tumors ◽

Positive Rate ◽

Grade Ii

Background: Cell cannibalism (cytophagocytosis) is defined as a tumor cell within a tumor cell, such that smaller tumor cells are found in the cytoplasm of larger tumor cells with crescent shaped nuclei. Aims and Objectives were to study the cytomorphological characters of cell cannibalism in primary and metastatic breast cancer, to correlate the histologic type and grade of tumors with positive rate of cannibalism and to study the role of Cannibalism as an independent prognostic factor in breast cancer.Methods: The study was conducted during the period of July 2003 to June 2005 in the Department of Surgery and Pathology, JNMCH, Aligarh. A total of 42 cases were included in the study. A minimum of 3 FNAC smears per case were assessed for cytophagocytosis. Presence of metastasis was also noted to establish the cytological grade and aggressiveness of the tumor.Results: Out of 42 cases, significant cannibalistic activity was noted in 30 (71.42%) cases. All grade III (33.4%) breast tumors were found positive for cytophagocytosis (4.28/smear), while the rate was much lower (2.33/smear) in grade II and (1.63/smear) in grade I tumors. LN metastasis was confirmed by histopathological examination in all high grade tumors showing significant cannibalistic activity.Conclusions: Cannibalism in breast carcinoma is an indicator of both the anaplastic grade and invasiveness. The rate of cytophagocytosis may have a prognostic significance.

Download Full-text

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

Cancers ◽

10.3390/cancers13040645 ◽

2021 ◽

Vol 13 (4) ◽

pp. 645

Author(s):

Damiano Cosimo Rigiracciolo ◽

Francesca Cirillo ◽

Marianna Talia ◽

Lucia Muglia ◽

Jorge Silvio Gutkind ◽

...

Keyword(s):

Breast Cancer ◽

Focal Adhesion Kinase ◽

Cancer Progression ◽

Focal Adhesion ◽

Breast Tumor ◽

Prognostic Significance ◽

Breast Tumors ◽

Breast Tumorigenesis ◽

Prognosis And Prediction ◽

Therapeutic Responses

Breast cancer represents the most common diagnosed malignancy and the main leading cause of tumor-related death among women worldwide. Therefore, several efforts have been made in order to identify valuable molecular biomarkers for the prognosis and prediction of therapeutic responses in breast tumor patients. In this context, emerging discoveries have indicated that focal adhesion kinase (FAK), a non-receptor tyrosine kinase, might represent a promising target involved in breast tumorigenesis. Of note, high FAK expression and activity have been tightly correlated with a poor clinical outcome and metastatic features in several tumors, including breast cancer. Recently, a role for the integrin-FAK signaling in mechanotransduction has been suggested and the function of FAK within the breast tumor microenvironment has been ascertained toward tumor angiogenesis and vascular permeability. FAK has been also involved in cancer stem cells (CSCs)-mediated initiation, maintenance and therapeutic responses of breast tumors. In addition, the potential of FAK to elicit breast tumor-promoting effects has been even associated with the capability to modulate immune responses. On the basis of these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. Here, we recapitulate the multifaceted action exerted by FAK and its prognostic significance in breast cancer. Moreover, we highlight the recent clinical evidence regarding the usefulness of FAK inhibitors in the treatment of breast tumors.

Download Full-text

Cytokeratin 7-Negative and GATA Binding Protein 3-Negative Breast Cancers: Clinicopathological Features and Prognostic Significance

10.21203/rs.2.11923/v2 ◽

2019 ◽

Author(s):

Shaolei Lu ◽

Evgeny Yakirevich ◽

Li Juan Wang ◽

Murray B Resnick ◽

Yihong Wang

Keyword(s):

Overall Survival ◽

Molecular Subtype ◽

Binding Protein ◽

Prognostic Significance ◽

Breast Tumors ◽

Clinicopathological Parameters ◽

Breast Cancers ◽

Cytokeratin 7 ◽

Gata3 Expression ◽

Grade 3

Abstract Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited. This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival. CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P=0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2 % of Grade 1 cases were GATA3 negative (P<0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor. This is the first study to characterize CK7 negative breast tumors in the context of clinicopathology.

Download Full-text

Cytokeratin 7-negative and GATA binding protein 3-negative breast cancers: Clinicopathological features and prognostic significance

BMC Cancer ◽

10.1186/s12885-019-6295-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Shaolei Lu ◽

Evgeny Yakirevich ◽

Li Juan Wang ◽

Murray B. Resnick ◽

Yihong Wang

Keyword(s):

Overall Survival ◽

Molecular Subtype ◽

Binding Protein ◽

Prognostic Significance ◽

Breast Tumors ◽

Clinicopathological Parameters ◽

Breast Cancers ◽

Cytokeratin 7 ◽

Gata3 Expression ◽

Grade 3

Abstract Background Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited. Methods This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival. Results CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P < 0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor. Conclusions This is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.

Download Full-text

Ultrastructural features of prognostic significance in human oral cancer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123490 ◽

1992 ◽

Vol 50 (1) ◽

pp. 618-619

Author(s):

Karvita B. Ahluwalia ◽

Nidhi Sharma

Keyword(s):

Oral Cancer ◽

Squamous Cell ◽

Common Knowledge ◽

Prognostic Significance ◽

Growth Control ◽

Terminal Differentiation ◽

Squamous Cell Carcinomas ◽

Effective Therapy ◽

Invasive Potential ◽

Biological Behaviour

It is common knowledge that apparently similar tumors often show different responses to therapy. This experience has generated the idea that histologically similar tumors could have biologically distinct behaviour. The development of effective therapy therefore, has the explicit challenge of understanding biological behaviour of a tumor. The question is which parameters in a tumor could relate to its biological behaviour ? It is now recognised that the development of malignancy requires an alteration in the program of terminal differentiation in addition to aberrant growth control. In this study therefore, ultrastructural markers that relate to defective terminal differentiation and possibly invasive potential of cells have been identified in human oral leukoplakias, erythroleukoplakias and squamous cell carcinomas of the tongue.

Download Full-text