Urothelial carcinoma of bladder (UBC), a highly prevalent urological malignancy associated with high mortality and recurrence rate. Standard diagnostic method currently being used is cystoscopy but ...its invasive nature and low sensitivity stresses for identifying predictive diagnostic marker. Autophagy, a cellular homeostasis maintaining process, is usually dysregulated in cancer and its role is still enigmatic in UBC. In this study, 30 UBC patients and healthy controls were enrolled. Histopathologically confirmed tumor and adjacent normal tissue were acquired from patients. Molecular expression and tissue localization of autophagy-associated molecules (HMGB-1, RAGE, beclin, LC-3, and p62) were investigated. Serum HMGB-1 concentration was measured in UBC patients and healthy controls. ROC curves were plotted to evaluate diagnostic potential. Transcript, protein, and IHC expression of HMGB-1, RAGE, beclin, and LC-3 displayed upregulated expression, while p62 was downregulated in bladder tumor tissue. Serum HMGB-1 levels were elevated in UBC patients. Transcript and circulatory levels of HMGB-1 showed positive correlation and displayed a positive trend with disease severity. Upon comparison with clinicopathological parameters, HMGB-1 emerged as molecule of statistical significance to exhibit association. HMGB-1 exhibited optimum sensitivity and specificity in serum. The positive correlation between tissue and serum levels of HMGB-1 showcases serum as a representation of in situ scenario, suggesting its clinical applicability for non-invasive testing. Moreover, optimum sensitivity and specificity displayed by HMGB-1 along with significant association with clinicopathological parameters makes it a potential candidate to be used as diagnostic marker for early detection of UBC but requires further validation in larger cohort.
Atrophic kidney-like lesion (AKLL) is a provisional renal entity with distinct morphological and immunohistochemical features. It characteristically resembles thyroid-like follicular renal cell ...carcinoma (RCC) of kidney, an emerging renal entity. Very few patients of AKLL have been reported in the literature. We are hereby describing the clinicopathological features of AKLL in a 38-year-old man. The patient was incidentally found to have a renal mass and underwent radical nephrectomy. The morphological and immunohistochemical findings revealed features of AKLL. The patient on 24 months’ post-operative period follow-up is alive without recurrence or metastasis.
ABSTRACT Purpose The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in ...prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. Materials and Methods This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. Results Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p <0.001) in prostate cancer tissue specimens. However, the expression of these miRNAs did not significantly differ in the urine of prostate cancer patients as compared to controls. Serum Prostatic Specific Antigen (PSA) inversely correlated with the median expression of miR-187 in prostatic tissue (p=0.002). Further, the expression of miRNA-187 in prostate cancer tissue was significantly decreased in metastatic prostate cancer (p=0.037). Using ROC analysis, miRNA-187 expression was able to distinguish the presence or absence of bone metastasis area under ROC (AUROC) (±SD) was 0.873±0.061, p <0.001. Conclusion The miRNA-182 and miRNA-187 appear to be promising biomarkers in prostate cancer and miRNA-187 can serve as an important diagnostic marker of metastatic prostate cancer.
Mucinous tubular and spindle cell renal cell carcinoma (MTSC-RCC) is a rare but favorable variant of renal cell carcinoma, predominantly found in adults. Complete surgical excision is the treatment ...of choice. We are reporting an intriguing case of bilateral MTSC-RCC in a 13-year-old-boy with rapid disease progression, leading to metastatic disease and subsequent demise of the child.
Carcinoma penis is a rare neoplasm, and the literature is scarce on long-term survival and its predictors. The aim of the study was to determine the clinical profile and management patterns, identify ...predictors of survival, and the impact of education and rural/urban dwelling on survival.
Patients with a histological diagnosis of carcinoma penis from January 2015 to December 2019 were included in the study. Demographics, clinical profile, education status, primary residence address, and outcomes were obtained from the case records. Distance from the treatment centre was obtained from the postal code. The primary objectives were to assess relapse-free survival (RFS) and overall survival (OS). The secondary objectives were to identify the predictors of RFS and OS and to determine the clinical profile and treatment patterns in patients with carcinoma penis in India. Time-to-event was calculated by Kaplan-Meir analysis and survival was compared by the log-rank test. Univariate and multivariable Cox regression analyses were used to find independent predictors of relapse and mortality. Logistic regression analyses to examine the associations of rural residence, education status, and distance from the treatment centre with the relapse adjusting for measured confounding variables.
Case records of 102 patients treated during the above period were retrieved. The median age was 55.5 (interquartile range IQR 42-65 years). Ulcero-proliferative growth (65%), pain (57%), and dysuria (36%) were the most common presenting features. Clinical examination or imaging revealed inguinal lymphadenopathy in 70.6% of patients, however, only 42% of these lesions were pathologically involved. A total of 58.8% of patients were from rural areas, 46.9% had no formal education, and 50.9% had a primary residence ≥100 km from the hospital. Patients with lower education and rural households had higher TNM stages and nodal involvement. Median RFS and OS were 57.6 months (15.8 months to not reached) and 83.9 months (32.5 months to not reached), respectively. On univariate analysis tumor stage, involvement of lymph nodes, T stage, performance status, and albumin was predictive for relapse and survival. However, on multivariate analysis, the stage remained the only predictor of RFS and nodal involvement, and metastatic disease was a predictor of OS. Education status, rural habitation, and distance from the treatment centre were not predictors for relapse or survival.
Patients with carcinoma have locally advanced disease at presentation. Rural dwellings and lower education were associated with the advanced stage but did not have a significant bearing on the survival outcomes. The stage at diagnosis and nodal involvement is the most important predictor of RFS and OS.
The recently recognized immunoglobulin G4 (IgG4)-related disease presenting as renal pelvic pseudotumor is rare. A definitive diagnosis is often difficult to obtain preoperatively, with patients ...being subjected to radical surgery due to suspicion of malignancy. We present a 64-year-old male with lower urinary tract symptoms, who, on evaluation had a right renal pelvic tumor on imaging and ureteroscopy. The patient underwent laparoscopic radical nephroureterectomy on clinical suspicion of upper tract urothelial carcinoma. The final histopathology revealed IgG4-related disease.
Epithelial-mesenchymal transition (EMT) plays an important role in bladder carcinoma (BC) invasiveness and metastasis. Studies have shown that muscle-invasive BC (MIBC) and non-MIBC (NMIBC) are ...different at the molecular level owing to different EMT-related programming. Recent studies suggest that dysregulation of specific miRNAs is linked to EMT in BC. With this background, we aimed to study the immunoexpression of EMT-markers and its correlation with miRNA-200c expression in a series of MIBCs and NMIBCs.
Quantitative real-time-polymerase chain reaction for the quantification of miR-200c expression was performed on 50 cases of urinary BC obtained from transurethral resection of bladder tumor (TURBT), cystectomy specimens, and ten peritumoral bladder tissue. Immunohistochemistry for ZEB1, ZEB2, TWIST, E-cadherin, and β-catenin was performed on tumor and peritumoral bladder tissue.
Thirty-five TURBT and 15 cystectomy specimens were assessed. Among MIBC, loss of expression of E-cadherin (72.3%), β-catenin (66.7%), and ZEB1, ZEB2, and TWIST2 immunoreactivity was noted in 53.3%, 86.7%, and 73.3% of cases, respectively. Among NMIBC, loss of expression of E-cadherin (22.5%), β-catenin (17.1%) and ZEB1, ZEB2, and TWIST immunoreactivity was noted in 11.5%, 51.4%, and 91.4% of cases, respectively. Upregulation of miRNA-200c was noted in cases with retained E-cadherin and negative TWIST expression. Downregulation of miRNA-200c expression was noted in all the cases showing loss of E-cadherin, β-catenin, and in cases immunoreactive for ZEB1, ZEB2, and TWIST in MIBC. Downregulation of miRNA-200c expression was also noted in cases of MIBC with retained β-catenin and those immunonegative for ZEB1 and ZEB2. A similar trend was noted in NMIBC. Median miRNA-200c expression was low in both high-grade and low-grade NMIBC compared to peritumoral bladder tissue and was not statistically significant.
This study for the first time explores the relation of miR200C with E-cadherin, b-catenin, and its direct transcriptional regulators, namely Zeb1, Zeb2, and Twist in the same cohort of BC. We observed that miRNA-200c is downregulated in both MIBC and NMIBC. We identified novel expression of TWIST in cases of BC showing downregulation of miR200Cs suggesting that it is one of the protein targets of altered miRNA-200c expression contributing to EMT and can serve as a promising diagnostic marker and therapeutic target. Loss of E-cadherin and ZEB1 immunoexpression in high-grade NMIBC suggests an aggressive clinical behavior. However, ZEB2 heterogeneous expression in BC limits its diagnostic and prognostic utility.
Background
The incidence of primary tracheal tumors is very low. Tracheal synovial sarcoma (SS) is even an extremely rare entity. Diagnosis of tracheal SS can be achieved with chromosomal ...translocation studies along with immunohistochemistry. Margin-free resection is the gold standard treatment.
Case presentation
We report a case of tracheal SS, which presented with stridor with a history of chronic cough and was diagnosed with a battery of clinical investigations and managed successfully with tracheal resection surgery. In histology, it may mimic Ewing’s sarcoma. Immunohistochemically, SS stains positive for cytokeratin, epithelial membrane antigen, vimentin, and S100. Chromosomal translocation t(X;18) (p11;q11) is found in almost all SS. This genetic signature is the gold standard diagnostic modality for these tumors.
Conclusion
Diagnosis of tracheal synovial sarcoma is challenging because of the rarity of the disease and common presenting symptoms to other tracheal pathology and is supplemented with chromosomal translocation study along with histopathology and immunohistochemistry. Tumor coring before definite surgical resection facilitates lung perfusion in obstructive tracheal pathology. A multidisciplinary team approach for diagnosis and management along with long-term follow-up are warranted.
Introduction: Human papillomavirus (HPV) is a known risk factor of penile cancer (PeCa). However, studies evaluating its true association are limited. In this study, we aimed to estimate HPV ...prevalence and its true association with PeCa in terms of molecular biological activities.
Materials and Methods: This single-institutional prospective observational study was conducted between June 2016 and August 2019. We included 40 men with PeCa as a study group and 20 age-matched uncircumcised men who underwent circumcision for phimosis as a control group. Both the groups underwent deoxyribonucleic acid isolation for HPV subtyping followed by evaluation of relative E6/E7 messenger ribonucleic acid (mRNA) expression profile and relative telomerase activity in tissue samples. HPV-16 and -18 were categorized as high-risk, whereas HPV-6 and -11 were categorized as low-risk subtypes.
Results: The mean (±standard deviation) age of PeCa was 51 ± 15.9 years. The majority of patients had stage II disease, and the most common procedure done was partial penectomy. The overall prevalence of HPV in PeCa was 42.5% (n = 17) as compared to 20% (n = 4) in controls. Among the subtypes, the most common subtype was HPV-16 noted in 33.3% (8/24) of cases, followed by HPV-18 in 29.2% (7/24) of cases. PeCa tissues had a significantly higher relative E7 mRNA expression for HPV-18 than the control group (P = 0.016). The mean relative telomerase activity was significantly higher in the PeCa tissues than the control group (138.66 vs. 14.46, P < 0.001). A significantly higher relative telomerase activity was noted in the PeCa tissues positive for high-risk HPV subtypes than controls (141.90 vs. 14.46, P = 0.0008), but not between high-risk HPV-positive and HPV-negative PeCa cases (141.90 vs. 137.03, P = 0.79). High-risk subtypes were not associated with tumor stage (P = 0.76) or lymph node metastasis (P = 0.816).
Conclusions: HPV was associated in 42.5% of PeCa cases based on our experience from a single institution. PeCa tissues had a higher relative E7 mRNA expression for HPV-18 and relative telomerase activity as compared to controls suggesting their potential role as surrogate markers of virus-induced tumorigenesis.
Objective: To evaluate bilateral superior and recurrent laryngeal nerves for tumor spread in patients of advanced-stage laryngeal carcinoma undergoing surgical resection. Methods: A prospective study ...was conducted including biopsy-proven cases of laryngeal squamous cell carcinoma (SCC) that were planned for total laryngectomy. Patients with metachronous or synchronous SCC were excluded from the study. All patients underwent total laryngectomy, where both superior and recurrent laryngeal nerves were harvested along with the specimen, and the proximal ends of the nerves were marked for reference. Perineural invasion (PNI) was assessed in nerves within the tumor and in bilateral extra-laryngeal nerves. Results: The study included 22 patients with a mean age of 58 years. Intra-tumoral PNI was found in 7 of the 22 cases (32%). The free nerve margins of superior and recurrent laryngeal nerves, which were examined from proximal to distal orientation, showed no tumor infiltration in any of the cases. Conclusion: Perineural invasion of minor nerves constitutes a major pathway of spread. On the contrary, invasion of superior or recurrent laryngeal nerves does not constitute a route for tumor spread. Hence, there is no need to extend the surgical boundary for total laryngectomy to include these major nerves separately. Keywords: Larynx cancer, squamous cell carcinoma, laryngectomy, recurrent laryngeal nerve, perineural spread
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