Immunotherapy, based on immune checkpoint inhibitors (ICIs) targeting the programmed cell death ligand 1 (PD-L1) and/or programmed death receptor 1 (PD-1), has substantially improved the outcomes of patients with various cancers. However, only ~30% of patients benefit from ICIs. Tumor PD-L1 expression, assessed by immunohistochemistry (IHC), is the most widely validated and used predictive biomarker to guide the selection of patients for ICIs. PD-L1 assessment may be challenging due to the necessity of different companion diagnostic assays for required specific ICIs and a relatively high level of inter-assay variability in terms of performance and cutoff levels. In this review, we discuss the role of PD-L1 IHC as a predictive test in immunotherapy (immuno-oncology), highlight the complexity of the PD-L1 testing landscape, discuss various preanalytical, analytical, and clinical issues that are associated with PD-L1 assays, and provide some insights into optimization of PD-L1 as a predictive biomarker in immuno-oncology.

Alpha-methylacyl-CoA racemase (AMACR/P504S) is a mitochondrial and peroxisomal enzyme involved in the branched-chain fatty acid and bile acid metabolism. AMACR is a useful diagnostic biomarker for prostate carcinomas and several other malignancies. Its expression in apocrine breast lesions had been previously reported, but its role in breast cancer progression has not been fully investigated. One hundred fifty breast samples (80 with invasive carcinomas) were studied. The expression of AMACR protein was analyzed using the immunohistochemical method (IHC). Lesions were considered positive if AMACR was detected in ≥10% of the cells at any intensity comprising a histologically defined normal epithelial structure or a pathologic lesion. In addition, AMACR mRNA relative expression was calculated from the whole-transcript RNA-Seq performed on >20,000 diverse tumor samples using a 20,000+ hybrid-capture NGS assay with the transcript capture panel based on the Agilent SureSelect Human All ExonV7. Expression of AMACR protein was restricted to epithelia. It was uncommon in the normal breast (7/81 samples, 9%). Increasing AMACR expression was observed with proliferative epithelial lesions (18% of usual ductal hyperplasias/adenosis, 70% of atypical lesions and 72% of DCIS/LCIS). Invasive ductal carcinomas NST and invasive lobular carcinomas expressed AMACR in 64% and 46%, respectively. The highest AMACR expression was observed in luminal B and HER2-positive breast carcinomas (86-100%). Triple-negative breast carcinomas exhibited AMACR in 50% of the cases. Apocrine lesions showed strong, nearly uniform overexpression of AMACR (100% of metaplasias, hyperplasias and in situ carcinomas and 88% of invasive apocrine carcinomas were positive). RNA-Seq analysis also confirmed AMACR expression in breast carcinomas, although its median value was substantially lower with a lower standard deviation than in prostate carcinomas. Over-expression of AMACR characterizes various proliferative, preinvasive and invasive breast lesions and is not specific to the apocrine morphology. It points to altered lipid metabolism (branched fatty acids) as one of the general characteristics of breast carcinogenesis, like several other malignancies. Its early detection may represent a potential target for cancer progression intervention.

No abstract available.

Aim A standardized assessment for the optimal repair of hypospadias remains elusive. The aim of this study was to assess a postoperative cosmetic outcome of hypospadias repair using a validated questionnaire, Hypospadias Objective Scoring Evaluation (HOSE). Methods During the period between January 2016 and May 2019, 40 patients who underwent hypospadias repair were identified and they agreed to a follow-up using the HOSE. Distal hypospadias repairs underwent a cross-sectional assessment of the cosmetic outcome. Cosmetic assessment was performed by an independent physician using the HOSE scoring system. Results The native meatus was coronal in 10 (25%), subcoronal in eight (20%), and distal penile in 22 (55%) patients. Mean followup was 35.90 months (SD ±29.58) postoperatively (range 12-162 months). Complications occurred in one (2.5%) patient. Out of 40 uncomplicated repairs, 39 (97.5%) were satisfactory. A vertical slit-like meatus located at the distal glans was created in 33 (82.5%) boys, and at the proximal glans in seven (17.5%). The urinary stream was single and straight in 39 and spray in one patient. A straight erection was observed in 39 (97.5%) boys. The median HOSE score was 16 (range 12-16). One patient had a small, single coronal fistula. The technique used included tubularised incised plate urethroplasty. Conclusion The HOSE score is simple, easy, non-invasive and non-expensive tool for objective assessment of long-term outcomes of hypospadias repair.

Juvenile cystic adenomyoma (JCA) is a rare uterine pathology with <40 cases reported in the current literature since 1996 when Tamura described it. We report a 13-year-old girl with a history of chronic pelvic pain and dysmenorrhea for 12 months. After diagnostic evaluation and identification of the cystic structure ( ∼ 6 cm) within the myometrium, fertility-sparing surgery was successfully performed. Histopathological examination of the uterine cyst was consistent with the diagnosis of JCA. The postoperative course was uneventful, and the patient was disease-free three years after surgery. JCA is a rare condition but should be considered in the differential diagnosis in adolescents with moderate to severe dysmenorrhea. Despite diagnostic advances, the awareness of the disorder remains low. Thus, our case report aims to increase awareness of this rare pathology with unclear etiology.

Simple Summary Recently, the interactions between microbiota and the host have been reported to induce the onset and progression of human cancer via epithelial–mesenchymal transition (EMT). In contrast, some microorganisms can protect against cancer growth, indicating an anticancer therapeutic action of such microbiota. In the review, we summarize findings from the literature, exploring the underlying mechanisms by which pathogenic microorganisms induce EMT. We also highlight the potential of exploiting these complex interactions for developing new biological therapies. Abstract Advancement in the development of molecular sequencing platforms has identified infectious bacteria or viruses that trigger the dysregulation of a set of genes inducing the epithelial–mesenchymal transition (EMT) event. EMT is essential for embryogenesis, wound repair, and organ development; meanwhile, during carcinogenesis, initiation of the EMT can promote cancer progression and metastasis. Recent studies have reported that interactions between the host and dysbiotic microbiota in different tissues and organs, such as the oral and nasal cavities, esophagus, stomach, gut, skin, and the reproductive tract, may provoke EMT. On the other hand, it is revealed that certain microorganisms display a protective role against cancer growth, indicative of possible therapeutic function. In this review, we summarize recent findings elucidating the underlying mechanisms of pathogenic microorganisms, especially the microbiota, in eliciting crucial regulator genes that induce EMT. Such an approach may help explain cancer progression and pave the way for developing novel preventive and therapeutic strategies.

Introduction: Human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and mouse mammary tumor virus-like virus (MMTV-like virus) can be present and contribute to breast cancer development and progression. However, the role of these oncoviruses and their crosstalk in breast cancer is still unclear. Methods: We explored the co-presence of high-risk HPVs, EBV, and MMTV-like virus in 74 breast cancer samples from Qatar using PCR. Results: We found the presence of HPV and EBV in 65% and 49% of our cancer sample cohorts; 47% of the samples are positive for both oncoviruses. The MMTV-like virus alone was detected in 15% of the samples with no significant association with clinicopathological features. The three oncoviruses were co-present in 14% of the cases; no significant association was noted between the co-presence of these viruses and the clinicopathological features. Conclusion: Despite the presence of the oncoviruses, additional studies are necessary to understand their interactions in human breast carcinogenesis.

c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis, and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.

Melanoma is a highly aggressive cancer originating from melanocytes. Its etiopathogenesis is strongly related to genetic, epigenetic, and environmental factors. Melanomas encountered in clinical practice are predominantly sporadic, whereas hereditary melanomas account for approximately 10% of the cases. Hereditary melanomas mainly develop due to mutations in the cyclin-dependent kinase 2A (CDKN2A) gene, which encodes two tumor suppressor proteins involved in the cell cycle regulation. CDKN2A, along with CDK4, TERT, and POT1 genes, are high-risk genes for melanoma. Among the genes that carry a moderate risk are MC1R and MITF, whose protein products are involved in melanin synthesis. The environment also contributes to the development of melanoma. Patients at risk of melanoma should be offered genetic counseling to discuss genetic testing options and the importance of skin UV protection, avoidance of sun exposure, and regular preventive dermatological examinations. Although cancer screening cannot prevent the development of the disease, it allows for early diagnosis when the survival rate is the highest.

Purpose Apocrine carcinoma of the breast (APO) expresses HER2 in 30–50% of cases. This study explored the clinicopathological features and outcome of HER2+/APO and matched HER2+/NST cohort. Methods We used the SEER database to explore the cohorts. Univariate and multivariate analyses were used to assess the survival. Based on ER and PR [steroid receptors/SR/] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons. Results We retrieved 259 cases of HER2+/APO. Most HER2+/APO were SR negative (65%). HER2+/APO were more prevalent in the 80+ age group (24.7% vs. 15.7%, p  < 0.001). HER2+/SR−/APO had a significantly lower histological grade than the HER2+/SR−/NST ( p  < 0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p  = 0.019). This was particularly evident between SR− subgroups (10.4% in HER2+/SR−/NST vs. 4.2% in HER2+/SR−/APO, p  = 0.008) and was reaffirmed in breast cancer-specific survival in univariate analysis ( p  = 0.03). Other than race and SR status, HER2+/APO subgroups did not differ in clinicopathological parameters. Conclusions Our study confirms the rarity of the APO and reveals that SR status in APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.