Yun Yi Kong

Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics

To evaluate the activation level of the mammalian target of rapamycin (mTOR) signalling pathway in Chinese patients with prostate cancer, as this pathway is over‐activated in many human cancers and is an attractive target for cancer therapy.

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a rare cytotoxic α/β T-cell lymphoma characterized by primary involvement of subcutaneous tissue mimicking panniculitis and a predominant CD3+/CD4−/CD8+ phenotype in 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas. We presented a detailed study of SPTL, describing clinicopathologic, immunophenotypic, and molecular features of 22 cases in China. Strict diagnostic criteria according to the WHO-EORTC definition were applied to the diagnosis of all SPTL cases. Besides the common features described before, unusual CD4+/CD8− and CD4−/CD8− T-cell phenotypes were noted in 2 of our cases, respectively. CD30 was negative in all cases and CD56 was focally positive in 2 cases. Mortality in cases with angioinvasion (75%) was significantly higher than that in cases without angioinvasion (14.3%). Epstein-Barr virus (EBV) infection was detected in 1 immunocompetent patient by in situ hybridization. The frequency of rearranged TCRB, TCRG, and TCRD genes detected by BIOMED-2 multiplex polymerase chain reaction tubes was 80%, 67%, and 13%, respectively, with a total clonality detection rate of 100%. Clinical follow-up was available in 18 patients, ranging from 6 to 80 months. Most patients obtained complete or partial remission after therapy including one accompanied with EBV infection; 5 patients died: 3 of disease progression, 1 of severe infection, and 1 of complications caused by diabetes and hypertension. We conclude that SPTL as a cytotoxic lymphoma derived from α/β T cell has a predominant CD4−/CD8+ phenotype, but unusual CD4+/CD8− and CD4−/CD8− phenotypes do exist. Owing to its indolent clinical course and relatively high survival rate, SPTL should be differentiated from cutaneous γ/δ T-cell lymphoma. EBV is generally absent in SPTL but can rarely be detected especially in Asian population. Angioinvasion is a poor prognostic factor in SPTL.

Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8 - 10 disease in prostatectomy specimens: Data from ethnic Chinese patients with localized prostate cancer

Study Type – Prognosis (prospective cohort)

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

This study aims to evaluate the potential value of patient characteristics in predicting overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time (PSADT), baseline haemoglobin (Hb) concentration, alkaline phosphatase (ALP) concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT <46.3 days and baseline ALP ≥ 110 IU l(-1), all patients were divided into three risk groups: low-risk group (no risk factors), intermediate-risk group (one risk factor) and high-risk group (two risk factors). Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months (95% CI: 23.8-32.2), 21.0 months (95% CI: 18.9-23.1) and 11.0 months (95% CI: 7.6-14.4), respectively (P<0.001). In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

Basal cell carcinoma of the scrotum: Clinicopathologic analysis of 10 cases

Background Basal cell carcinoma (BCC) located on the scrotum is rare. Objective To analyze clinical and pathologic features, discuss therapeutic strategies, and identify prognostic factors of scrotal BCC in Chinese patients. Materials and Methods Between 2000 and 2010, 10 patients with scrotal BCC were diagnosed and treated at our institution. A review was performed using the clinical records and dermatopathologic slides of these patients. Results The median patient age was 70. Skin lesions presented as red nodules and brownish plaques. All patients were treated using wide excision without adjuvant therapy. After an average follow‐up of 47 months, eight patients were in good health without any relapse. One patient developed left inguinal lymph node metastasis at 21 months that was successfully treated using bilateral inguinal lymphadenectomy. One patient developed bilateral pulmonary metastasis at 48 months and was palliatively treated with chemotherapy. The clinical and histopathologic risk factors predisposing to metastasis were large primary neoplasms; a long period of misdiagnosis; and infiltrating, morpheaform, spiky, irregular outline pathologic patterns. Conclusions BCC of the scrotum is rare. It can metastasize after a long period of initial therapy. Long‐term surveillance including a complete metastatic examination is recommended for these patients.

Primary invasive carcinoma associated with penoscrotal extramammary Paget's disease: a clinicopathological analysis of 56 cases

To investigate the clinicopathological features, therapeutic strategies, and prognostic factors of patients with penoscrotal invasive extramammary Pagets disease (EMPD).

Analysis of KIT expression and gene mutation in human acral melanoma: With a comparison between primary tumors and corresponding metastases/recurrences

KIT mutations play an important role during the pathogenesis of melanoma. Acral melanoma, which is the most common type in China, is more likely to harbor activating KIT mutations. Currently, there are few large studies on KIT expression and mutation in acral melanoma, especially in patients with matched primary/secondary pairs. Here, we investigated KIT expression and mutation in 39 primary acral melanomas together with their corresponding secondary tumors (17 lymph node metastases, 6 local recurrences, and 3 skin metastases) and explored the relationship between KIT expression, mutation, and clinicopathologic characteristics. Cytoplasmic and membranous staining for KIT was noted in 17 cases (43.6%) of 39 primary acral melanomas. KIT expression in patients without lymph node metastases at presentation was significantly higher than those with lymph node metastases (P = .024). KIT mutations were detected in 9 (23.1%) of 39 cases of primary acral melanomas. KIT expression did not correlate with KIT mutation status. In 23 cases with primary/secondary pairs, KIT mutations were observed in 6 cases. Comparison of KIT mutations between primary and secondary tumors showed a discordance rate of 13.0% (3/23). We concluded that KIT mutations are common in acral melanoma, and patients with acral melanoma should be screened for KIT mutations. Mutation status may change during metastases/recurrences after diagnosis of primary tumors. This has important clinical implications, and its mechanism needs further investigation.

Combination of circulating tumor cell enumeration and tumor marker detection in predicting prognosis and treatment effect in metastatic castration-resistant prostate cancer

Although circulating tumor cell (CTC) enumeration in peripheral blood has already been validated as a reliable biomarker in predicting prognosis in metastatic castration-resistant prostate cancer (mCRPC), patients with favorable CTC counts (CTC < 5/7.5 ml) still experience various survival times. Assays that can reduce patients risks are urgently needed. In this study, we set up a real-time quantitative polymerase chain reaction (RT-qPCR) method to detect epithelial-mesenchymal transition (EMT) and stem cell gene expression status in peripheral blood to validate whether they could complement CTC enumeration. From January 2013 to June 2014 we collected peripheral blood from 70 mCRPC patients and enumerated CTC in these blood samples using CellSearch system. At the same time, stem cell-related genes (ABCG2, PROM1 and PSCA) and EMT-related genes (TWIST1 and vimentin) were detected in these peripheral blood samples using an RT-qPCR assay. Patient overall survival (OS) and treatment methods were recorded in the follow-up. For patients who received first-line chemotherapy, docetaxel plus prednisone, PSA progression-free survival (PSA-PFS) and PSA response rate were recorded. At the time of analysis, 35 patients had died of prostate cancer with a median follow-up of 16.0 months. Unfavorable CTC enumerations (CTC ≥5/7.5 ml) were predictive of shorter OS (p = 0.01). Also, positive stem cell gene expression indicated poor prognosis in mCRPC patients (p = 0.01). However, EMT gene expression status failed to show any prognostic value in OS (p = 0.78). A multivariate analysis indicated that serum albumin (p = 0.04), ECOG performance status (p < 0.01), CTC enumeration (p = 0.02) and stem cell gene expression status (p = 0.01) were independent prognostic factors for OS. For the 40 patients categorized into the favorable CTC enumeration group, positive stem cell gene expression also suggested poor prognosis (p < 0.01). A combined prognostic model consisting of stem cell gene expression and CTC enumeration increased the concordance probability estimated value from 0.716 to 0.889 in comparison with CTC enumeration alone. For patients who received docetaxel plus prednisone as first-line chemotherapy, positive stem cell gene expression suggested a poor PSA-PFS (p = 0.01) and a low PSA response rate (p = 0.008). However, CTC enumeration and EMT gene expression status did not affect PSA-PFS or PSA response rates. As a result, detection of peripheral blood stem cell gene expression could complement CTC enumeration in predicting OS and docetaxel-based treatment effects in mCRPC patients.

Relationship between circumcision and human papillomavirus infection: a systematic review and meta-analysis

Male circumcision (MC) is reported to reduce human papillomavirus (HPV) prevalence in men. However, the efficacy remains imprecise. The aim of this study was to conduct a systematic review and meta-analysis to assess the relationship between MC and genital HPV infection and genital warts. PUBMED, EMBASE, and Web of Science were searched from inception to March 22, 2015. We identified 30 papers, including a total of 12149 circumcised and 12252 uncircumcised men who were evaluated for the association of circumcision with genital HPV or genital warts. Compared with men who were not circumcised, circumcised men may have had significantly reduced odds of genital HPV prevalence (odds ratio [OR]: 0.68; 95% confidence interval [95% CI]: 0.56-0.82). There was no significant association between MC and genital HPV acquisition of new infections (OR: 0.99; 95% CI: 0.62-1.60), genital HPV clearance (OR: 1.38; 95% CI: 0.96-1.97), and prevalence of genital warts (OR: 1.17; 95% CI: 0.63-2.17). This meta-analysis suggests that circumcision reduces the prevalence of genital HPV infections. However, no clear evidence was found that circumcision was associated with decreased HPV acquisition, increased HPV clearance, or decreased the prevalence of genital warts. More studies are required to evaluate adequately the effect of MC on the acquisition and clearance of HPV infections and prevalence of genital warts.

Intravascular large B-cell lymphoma with cutaneous manifestations: a clinicopathologic, immunophenotypic and molecular study of three cases

Background:u2002 Intravascular large B‐cell lymphoma (IVLBCL) is an extremely rare type of malignant lymphoma characterized by exclusive or predominant growth of neoplastic cells within the lumen of blood vessels. Cases in the literature predominantly involve the skin and central nervous system, with special emphasis on the ‘cutaneous variant’.