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Background: Inflammatory breast cancer is a highly aggressive form of breast cancer that robustly forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. Inflammatory breast cancers express high levels of E-cadherin, the major protein of adherens junctions, which may enhance the ability of tumor cells to form such clusters and contribute to metastasis. Seemingly contradictory, E-cadherin has both tumor-suppressing and tumor-promoting roles in cancer; previous studies suggest that this depends on the balance between apical and basolateral cadherin-catenin complexes. Methods: In the present study, we use immunohistochemistry of inflammatory breast cancer patient samples and biochemical analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We use viral transduction to ectopically express PLEKHA7 in the SUM149 inflammatory breast cancer cell line. The effect of PLEKHA7 on the aggressiveness of inflammatory breast cancer in 2D, 3D and in-vivo were examined. Results: We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in a strong majority of patient samples and very low expression in cell line models. We found that re-expressing PLEKHA7 is sufficient to suppress proliferation, anchorage independent growth, spheroid viability, and tumor growth in-vivo. We also observed a negative-selection pressure within the xenograft tumors to lose PLEKHA7 function or expression.Conclusions: The data indicate that PLEKHA7 is frequently deregulated and acts as a suppressor of inflammatory breast cancer. They also suggest that the resulting imbalance between apical and basolateral cadherin-catenin complexes contributes to growth, survival and emboli-forming capacities of inflammatory breast cancer.

Non-neoplastic diseases of the anus encompass a variety of lesions which include inflammatory processes such as anorectal infections and involvement by inflammatory bowel disease. The most common causes of anorectal infections are sexually transmitted infections with pathogens such as herpes simplex virus and Treponema pallidum (syphilis). An increase in proportion of these infections has been observed in recent years. This chapter highlights the pathognomonic features of these infections which will be useful to the pathologist for accurate diagnosis and hence early treatment and prevention of further transmission. Anal canal is involved in a significant proportion of patients with Crohn’s disease. In a small subset of patients, anal canal is the only site involved at presentation. Various chronic and debilitating manifestations of Crohn’s disease are discussed which include anal fissures, strictures, and fistulas. Pathological features of other benign lesions such as fibroepithelial polyps, inflammatory cloacogenic polyp, hemorrhoids, and anal abscesses are also discussed.