Spontaneous CD4+ and CD8+ T-cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients.

Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8+ and CD4+ T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8+ T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype.

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: An Observational Study.

Triple negative breast cancer (TNBC) is a phenotype of breast cancer with aggressive clinical behavior. Because of the absence of optimal treatment, the prognosis of this disease is poor. The main purpose of this study was to detect the response to neoadjuvant chemotherapy (NACT) in a TNBC cohort and compare the long-term survival between patients with and without pathological complete response (pCR). A total of 53 patients diagnosed with TNBC from 2005 to 2013 who received NACT at the University Hospital Birmingham were enrolled in this study. Overall survival (OS) and progression-free survival (PFS) were compared between the pCR group and non-pCR group. Demographic information and clinical or pathologic parameters were also analyzed to explore potential predictive and prognostic factors. Fourteen patients (26.4%) achieved pCR to NACT. In univariate analysis, patients with pCR had longer PFS time (p = 0.013) and OS time (p = 0.054) compared with their counterparts without pCR. In multivariate analysis, the existence of lymphovascular invasion (LVI) significantly reduced OS (HR = 17.404, 95% CI = 2.923-103.644) and PFS (HR = 7.776, 95% CI = 1.645-36.753). The achievement of pCR to NACT can significantly postpone the incidence of disease progression in patients with TNBC. There is not enough evidence showing its influence on ultimate survival. LVI may be a more potent prognostic factor than pCR in the TNBC cohort.

Lack of CD151/integrin α3ß1 complex is predictive of poor outcome in node-negative lobular breast carcinoma: opposing roles of CD151 in invasive lobular and ductal breast cancers.

BACKGROUND: The proposed involvement of CD151 in breast cancer (BCa) progression is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and invasive lobular carcinoma (ILC) represent distinct disease entities. Here we evaluated clinical significance of CD151 alone and in association with integrin α3ß1 in patients with ILC in context of the data of our recent IDC study. METHODS: Expression of CD151 and/or integrin α3ß1 was evaluated in ILC samples (N=117) using immunohistochemistry. The findings were analysed in relation to our results from an IDC cohort (N=182) demonstrating a prognostic value of an expression of CD151/integrin α3ß1 complex in patients with HER2-negative tumours. RESULTS: Unlike in the IDCs, neither CD151 nor CD151/α3ß1 complex showed any correlation with any of the ILC characteristics. Lack of both CD151 and α3ß1 was significantly correlated with poor survival (P=0.034) in lymph node-negative ILC N(-) cases. The CD151(-)/α3ß1(-) patients had 3.12-fold higher risk of death from BCa in comparison with the rest of the ILC N(-) patients. CONCLUSIONS: Biological role of CD151/α3ß1 varies between ILC and IDC. Assessment of CD151/α3ß1 might help to identify ILC N(-) patients with increased risk of distant metastases.

Malakoplakia of the Urogenital Tract.

Malakoplakia is a rare, granulomatous condition most commonly found in the genitourinary tract. It can present in a myriad of ways depending on the organ involved, thus presenting a huge diagnostic challenge. We present 4 patients with genitourinary malakoplakia, who manifested with recurrent urinary tract infection (UTI) and hematuria in all except one, who presented with hydronephrosis secondary to a large pelvic mass. We discuss the need for a high index of suspicion and careful scrutiny of histology to order to avoid misdiagnosis as simple long term antibiotics are an effective treatment in all but those with large pelvic masses.

T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6.

BACKGROUND: Evidence suggests that some patients with renal cell carcinoma (RCC) respond to immunomodulatory therapies that activate T lymphocytes. A prerequisite for effective T cell therapy is efficient targeting of effector T cells to the tumour site, yet the molecular basis of T cell recruitment to RCC is unknown. Furthermore, some T cells that naturally infiltrate this cancer are regulatory T cells (Tregs) that may suppress antitumour immune responses. OBJECTIVE: Determine the mechanisms of effector and regulatory T cell recruitment to RCC to allow targeted therapy that promotes local anti-tumour immunity. DESIGN, SETTING, AND PARTICIPANTS: Tumour-infiltrating and peripheral blood T cells were collected from 70 patients undergoing nephrectomy for RCC. MEASUREMENTS: T cells were analysed by multicolour flow cytometry for expression of 19 chemokine receptors and 7 adhesion molecules. Receptors that were expressed at higher levels on tumour-infiltrating lymphocytes (TILs) compared with matched peripheral blood lymphocytes (PBLs) were analysed further for their ability to mediate migration responses in TILs and for expression of corresponding ligands in tumour tissue. RESULTS AND LIMITATIONS: Three chemokine receptors-CCR5, CXCR3, and CXCR6-were significantly overexpressed on TILs compared with matched PBLs (n=16 cases) and were capable of promoting migration in vitro. Their corresponding ligands CCL4-5, CXCL9-11, and CXCL16 were all detected in RCC tissue. However, since they were present in all cases studied, it was not possible to correlate ligand expression with levels of T cell infiltration. Foxp3(+) Tregs were enriched within TILs compared with matched PBLs and expressed high levels of CCR5, CXCR3, and CXCR6, as well as CCR6, the ligand for which (CCL20) was detectable in RCC tissue. CONCLUSIONS: Our data support a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into RCC tissue and, together with CCR6, in the recruitment of Tregs.

Metastatic serous carcinoma of the testis: a case report and review of the literature.

Serous tumours of the testis and paratestis are rare, with fewer than 50 cases reported in the literature. The majority of the reported cases have been borderline serous tumours, and these tend not to recur or metastasize. Conversely, serous carcinomas can metastasize but this is often a late event. The presence of invasion in an otherwise borderline tumour has also been associated with the development of metastatic disease several years later, thus highlighting the importance of extensive sampling of all cases of borderline serous tumours. We report a case of a young man diagnosed with serous carcinoma of the testis, occurring 18 years after first diagnosis of a testicular germ cell tumour in the contralateral testis. This pattern has not previously been reported.

Sorafenib induces therapeutic response in a patient with metastatic collecting duct carcinoma of kidney.

BACKGROUND: Collecting duct carcinoma (CDC) is a rare and aggressive variant of renal cell carcinoma (RCC), which has poor response to cytokine therapy and chemotherapy. Introduction of tyrosine kinase inhibitors (TKIs), in particular sorafenib and sunitinib, is changing the treatment paradigm for management of RCC. However, patients with CDC have been excluded from the majority of randomised trials involving the use of TKIs. CASE REPORT: Our patient with metastatic CDC was treated with sorafenib, and demonstrated an excellent response, both clinically and radiologically. She continues on sorafenib treatment with minimal toxicity, and has demonstrated a progression-free survival exceeding 13 months. CONCLUSIONS: This is the first reported case of a patient with CDC responding to sorafenib treatment. Therefore, the role of sorafenib in the management of metastatic CDC needs prospective evaluation.

Morphologic changes in the endometrium associated with the use of the mirena coil: a retrospective study of 106 cases.

This study outlines the histologic changes seen in 106 endometrial specimens after use of the Mirena coil (levonorgestrel) and compares these changes with previous studies. The variables assessed include nature of the endometrial glands, metaplastic glandular changes, nuclear atypia, hobnail change, and endometrial hyperplasia. Stromal changes include pseudodecidualization, mucinous change, ulceration, and infiltration by granulocytes, neutrophils, and plasma cells, and stromal hyaline nodules, a feature not described previously. Additional changes include superficial micropapillary change, infarcted decidua, dystrophic calcification, hemosiderophages, polypoid indentations, cervical microglandular hyperplasia and endocervical pseudodecidualization. These variables are compared with a similar previous study. Significant differences in the incidence of glandular metaplasia, dystrophic calcification, plasma cell infiltrates, hemosiderophages, and presence of nuclear atypia are noted. With increased use of the Mirena coil, histopathologists need to be aware of the characteristic and constant endometrial changes due to progestogenic and mechanical effects, despite a wide variation in the duration of usage.