Breast cancer and dermatomyositis: a case study and literature review.

A 49-year-old woman presents with an extensive violaceous rash, rapidly progressive proximal muscle weakness, and dysphagia to solids, consistent with a diagnosis of dermatomyositis. Two weeks later, she palpates a mass in her left breast and is diagnosed with her2-positive metastatic invasive ductal carcinoma of the breast. There is a well-established association between dermatomyositis and malignancy. However, the specific association between breast cancer and dermatomyositis has not been well characterized. No guideline for oncologists managing these patients has been established. Recently, 3 cases of breast cancer and dermatomyositis were diagnosed at our institution. A review of the literature was pursued to characterize the association between breast cancer and dermatomyositis. A review of 178 papers identified 22 cases of breast cancer with dermatomyositis. Most patients (71%) presented with stage iii or iv breast cancer. The median time between the diagnosis of breast cancer and the onset of dermatomyositis symptoms was 1 month. Three quarters of the patients were steroid-responsive and able to taper. Half the women with follow-up data experienced a documented cancer relapse associated with a new flare of cutaneous symptoms. The presence of dermatomyositis appears to be associated with more-advanced breast cancer stage and is most commonly associated with invasive ductal carcinoma. In our review, treatment of cancer alone is insufficient to adequately control the cutaneous and myopathic manifestations of dermatomyositis, which can significantly affect quality of life. A multidisciplinary approach, including close collaboration with rheumatologists and dermatologists, is therefore important in the diagnosis and management of oncology patients with dermatomyositis.

Malignancies in a renal transplant population: The St. Michael's Hospital experience.

INTRODUCTION: Previous publications have shown an increased incidence of various malignancies amongst renal transplant populations. The objective of this study was to analyze the rate and types of malignancies occurring in the St. Michael's Hospital renal transplant population and to determine whether our results were comparable to those previously published. METHODS: After approval by the hospital's research ethic board, review of the records and pathology of the 1584 patients in the renal transplant clinic database patients was performed. The reports dated back to the year 1970. RESULTS: Amongst the 1584 renal transplant patients, 106 patients with 132 dysplastic and malignant posttransplant lesions were identified. The highest incidence amid the malignancies was in nonmelanoma skin malignancies squamous cell carcinoma (SCC), basal cell carcinoma, and Kaposi sarcoma, with a total of 32 patients having 54 separate tumors (2.02% of all patients, 43.2% of tumors). Following skin tumors in incidence were genitourinary (28 tumors), gastrointestinal tract (GIT) lesions (8 adenocarcinomas, 14 dysplastic lesions, 1 low grade neuroendocrine tumor/carcinoid), posttransplant lymphoproliferative disorders (PTLDs) (10 cases), gynecologic (6 carcinomas), cervical/anal/vulvar dysplasia and invasive (SCCs) (4), and thyroid (3 papillary tumors). Nine patients had tumors of multiple sites/types. With respect to outcome, 14 patients died of malignancy, with the highest mortality being in the GIT malignancies (six patients). Second in mortality were the PTLD and skin tumor groups. DISCUSSION: Information on the incidence and outcome of various malignancies in renal transplant patients is important in designing guidelines for the follow-up of these patients regarding tumor screening and prevention. The rate of malignancies in our group is comparable to that reported in other centers.

Malignancies arising in allograft kidneys, with a first reported translocation RCC post-transplantation: A case series.

BACKGROUND: The increased risk of malignancy in the post-renal transplant population has been well documented. Renal carcinoma is more common in this population, usually arising in native kidneys. Rarely, tumors arise in the transplanted kidney. Our case series reports four cases of malignancy in allograft kidneys, one of which is a first reported case of translocation RCC in a transplanted kidney. METHODS: The renal transplantation database (1584 patients) at St. Michael's Hospital was reviewed for malignancies arising in allograft kidneys: reports and pathology slides were reviewed. RESULTS: Four cases of malignancies arising in the allograft kidney were identified among our kidney transplant population. One patient developed a high grade urothelial carcinoma in the donor kidney post BK virus infection. The other 3 cases were renal cell carcinomas: one clear cell renal cell carcinoma, one translocation renal cell carcinoma, and one papillary renal cell carcinoma. The translocation renal cell cancer had confirmed TFE3 protein over-expression by immunohistochemistry. Molecular testing of the tumors in all 4 cases identified two separate genetic profiles, favored to represent tumors arising from donor tissues along with infiltrating recipient lymphocytes. DISCUSSION: Previous reports suggested that epithelial malignancies in allograft kidneys are rare. We identified 4 such tumors in 1584 transplant patients. Further, we identified the first reported case of translocation RCC in an allograft kidney. While the rate of malignancy in allograft kidneys is low, screening of the donor kidneys by ultrasound and/or urine cytology may be of use in detecting these lesions.

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer.

BACKGROUND: Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. METHODS: We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR-KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3' untranslated region (UTR), pMIR-KLK10, and measuring KLK10 protein levels after transfection with miRNA. RESULTS: When we co-transfected cells with pMIR-KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. CONCLUSION: Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.