Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel protein.Its expression is restricted to prostate epithelial cells.The exact function is unknown.This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells.ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative vs.strong ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa.ANO7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa.

Liposarcoma of the breast arising in a malignant phyllodes tumor:A case report and review of the literature

Liposarcoma of the breast is a very rare malignant tumor. It can clinically manifest as a palpable breast mass and mimic primary breast cancer. We report an unusual case of a 51-year-old female who presented with an asymptomatic right breast mass, which was histologically diagnosed as well differentiated liposarcoma arisen within malignant phyllodes tumor. The patient underwent breast conserving surgery, received no adjuvant treatment and is disease-free after 2 years. Radiological and histopathological features are presented and described in detail. Data from the literature are presented and therapy recommendations discussed.

Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers

Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia;however, it was downregulated in 48% and negative in42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression(P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis(P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52%in pT3 b-pT4(P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8(P <0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect(P < 0.0001).However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10%(P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.

Male papillary breast cancer treated by wide resection and latissimus dorsi flap reconstruction: A case report and review of the literature

Breast cancer(BC) in men represents between 0.5% and 1% of all BC diagnosed each year. We report a case of advanced BC in a 62-year-old male treated at our interdisciplinary Breast Cancer Center. The patient presented with a newly diagnosed large, symptomatic mass in his left breast. Clinical examination showed a not movable mass of 16 cm diameter, deforming the whole breast; the overlying skin was livid and hypervascularized. Enlarged lymph nodes were palpable in the axillary pit. He had no concomitant diseases at time of presentation. He denied any first- or second degree family medical history of cancer of any type and he never received radiotherapy. Ultrasound guided minimal-invasive 14-gauge core biopsy revealed a moderately differentiated encapsulated papillary carcinoma with high expression of estrogen and progesterone receptors(both > 80%, IRS 12) and HER2-negative. Because of the tumor size a mastectomy with axillary dissection and chest wall reconstruction using a latissimus dorsi flap was performed. Histological analysis showed invasive growth besides typical(non-invasive) papillary carcinoma and was classified as invasive solid papillary carcinoma; p T3(10 cm), p N0(0/15), M0,R0; Oncotype DX Recurrence Score indicated low risk(RS: 2). After discussion in the interdisciplinary tumor board meeting, radiation therapy and tamoxifen were recommended. The patient had an uneventful recovery and is disease-free after two years of follow-up. Male BC is typically diagnosed at an advanced stage, most likely due to a lack of awareness that men can develop BC. Therefore, in case of a large tumor, a flap-based thoracic reconstruction may be required.

CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human intestines.While CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.