Focal Adhesion Kinase Induces Matrix Metalloproteinase-2 by Involving α5β1-Mediated Signaling in Breast Cancer Cell, MCF-7.

Introduction: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a pivotal role in cell invasion. Matrix metalloproteinases (MMPs) are implicated as the key players in cancer cell invasion. Hence, the role of FAK in MMP regulation is very important in understanding tumor progression. Materials and Methods: Here, we studied the role of FAK, its association with other signaling kinases and involvement in the α5β1 integrin receptor-mediated regulation of MMP-2 activity and expression in human breast cancer cell line MCF-7. Results: Immuno blot analysis revealed that FN treatment causes phosphorylation of FAK and FAK gets localized at the cell attachment focal point of MCF-7 cells. FN treatment did not change the mRNA status of FAK but enhanced mRNA level of MMP-2 and MT1-MMP, also caused downregulation of TIMP-2. Co-imunoprecipitation and inhibitor studies revealed the association of FAK with α5β1, Paxillin, PI3K and ERK. siRNA studies revealed that FAK is critical in regulation of activity and expression of MMP-2 and downstream signaling kinases. Conclusion: Th e interaction of α5β1 integrin with FN initiates a signaling cascade with FAK as its central player. FAK gets phosphorylated and in turn associates with tyrosine kinases like PI3K and ERK. FAK also activates PI3K and ERK that serve as very crucial mediators of the signaling pathway leading to induction of MMP-2 activity and resulting invasion of breast cancer cell, MCF-7.

CD44: A key player in breast cancer.

CD44 is a principal transmembrane hyluronate receptor, which acts as a hook between Extracellular Matrix and the cytoskeleton. CD44 is up regulated in breast cancer, which in turn helps in tumor progression and metastasis. There has been a lot of attention given to CD44 in recent years because of the discovery, CD44+/CD24- lineage marks breast cancer stem cells. Recent clinical and experimental findings show that CD44 is involved in the tumor associated proliferation, invasion, migration, and in many pathways involved in maintaining cancer cells which inturn are correlated with patient's survival. All these findings make CD44 as a potential target for breast cancer treatment. The methods of literature search for this article include Pubmed, BMC cancer and other printed journal article.

Breast Fine Needle Aspiration Cytology Reporting : A Study of Application of Probabilistic Approach.

Background: This study is based on application of probabilistic approach in reporting of breast fine needle aspiration cytology, its accuracy and correlation with likelihood of carcinoma in histology. Material and Method: Breast cytology was reported according to 1 of 6 categories, positive, suspicious, atypical, proliferative without atypia, unremarkable and unsatisfactory. Histologic correlation was done whenever possible. Results: Out of total 515 cases, 138 were correlated in histology. There were no false positive cases. The probability of finding carcinoma on histology, for suspicious and atypical categories was 94.11% and 75% respectively. All lesions from proliferative without atypia and unremarkable categories were benign on histology. Conclusion: The probabilistic approach is uniform, accurate method and easy to apply in reporting of breast FNAs. Suspicious and atypical categories were associated with increased incidence of carcinoma in histology and therefore such cases should be further evaluated for histology.

Cytohistopathological Correlation in Palpable Breast Lesions.

The objective was to study the correlation between cytological and histopathological features and to find out the sensitivity and specificity of Fine Needle Aspiration Cytology (FNAC) in the diagnosis of breast lesions. Two hundred patients were studied; 150 were retrospective and 50 were prospective cases. Only those patients who had FNAC followed by histopathological examination were included. Useful cytological parameters for diagnosis of malignancy were loss of cell cohesion, cell size, nuclear crowding and overlapping, nuclear size, type of chromatin, absence of bipolar naked nuclei and infiltration of stroma. In present study complete sensitivity was 96.2%, absolute sensitivity was 86.7%, predictive value was 100%, false negative were 1.9%. No false positive smear was seen. We concluded that a definitive diagnosis of malignancy by FNAC could be safely used for definitive treatment but the same was not true for non-malignant, suspicious or atypical smears. In these situations surgical biopsy was considered to be essential for definitive diagnosis.

Reliability of Fine Needle Aspiration Cytology (FNAC) in Very Small Breast Lumps.

FNAC diagnosis and subsequent histopathology of 166 breast lumps of different sizes, depth and mobility were studied prospectively over a 10-year period (1990-2000) and grouped into two groups. Group-I of lumps <2cm and Group-II of lumps >2cm (control 80 cases). They were again subclassified as deep or not deep and mobile or fixed. Statistically significant positive correlation was found in all categories for less accurate diagnosis of lumps of <2 cm as compared to those of >2 cm. Therefore, because of low diagnostic accuracy in Group- I, it is recommended that for lumps <2cm even if the FNAC diagnosis is “non-malignant” a lumpectomy histopathological examination be done.