Assessment of Utility of Immunohistochemical Marker Prostein for Evaluation of Primary and Metastatic Prostatic Carcinomas

Background: To assess utility of immunohistochemical marker prostein for evaluation of primary and metastatic prostatic carcinomas.Methods:Fifty- six samples of clinically suspected carcinoma prostate was included. Immunohistochemistry (IHC) was performed for assessment of Prostein (P501S). The intensity of positivity was scored from 0 to 3 as follows: score 0 = non-stained; score 1 = weak; score 2 = moderate; and score 3 = strong. The percentage of positively stained cells for each staining intensity was estimated in the respective lesions.Results:Age group 18-28 years comprised of 6 patients, 28-38 years had 12, 38- 48 years had 16 and >48 years had 22 cases. Type of cases were normal prostatic epithelium in 11, benign prostate hyperplasia in 23, HGPIN in 10, primary prostatic adenocarcinoma in 7 and metastatic prostatic adenocarcinoma in 5 cases. Prostein expression was seen in 100% in normal prostatic epithelium with intensity score of 1.8-2.1, benign prostate hyperplasia having 2-2.7, HGPIN with 2-2.3, primary prostatic adenocarcinoma having 1-1.6 and metastatic prostatic adenocarcinoma with 0.8-1.4 intensity score. Conclusion:Prostein is a new prostate specific marker which showed 100% sensitivity and specificity to identify normal and prostatic lesions.

Correlation between serum PSA, gleason score and histopathological grading of adenocarcinoma of prostate in patients undergoing TRUS guided prostatic biopsy in a tertiary care centre of Southern India

Background Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths worldwide. Serum psa, a glycoprotein and a serine protease, which is increased in all prostatic diseases but markedly elevated levels are indicative of carcinoma prostate. The present study was done to evaluate the histopathologyof carcinoma of prostate in trus guided prostatic biopsy specimens and correlate serum psa levels with gleason score and grade groups. Methods A hundred patients presented with luts and suspicious of carcinoma prostate underwent trus guided 16 core prostatic biopsy. Histopathological examination, gleason scores and grades of biopsies were obtained. Based on the gleason scores, patients with carcinoma of the prostate were divided into five-grade groups. Mean serum psa levels were calculated and correlated with gleason score and grade groups. Results Malignancy was found in 69 per cent of cases, of which 68 patients were found to have adenocarcinoma of the prostate, one patient found to have undifferentiated carcinoma of the prostate. The total number of patients in each gleason grade groups were obtained, and the mean serum psa levels of these patients in each group were calculated. Mean serum psa levels in each group are group 1 (21.3 ng/ml), group 2 (58.4 ng/ml), group 3 (73.6 ng/ml), group 4 (118.4 ng/ml), group 5 (96.3 ng/ml). Conclusion Serum psa is a highly sensitive tumour marker with low specificity, and its levels are increased in many benign and iatrogenic conditions. Psa has a high negative predictive value which is essential in ruling out malignancy. In our study, higher serum psa levels were correlated with higher gleason score and grades.

Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.

Metastasis to spermatic cord from carcinoma prostate: A case series

Despite the high incidence of secondaries to lymph nodes, bones, and lungs in carcinoma (CA) prostate, metastatic involvement of scrotal organs is rare and usually associated with a poor prognosis. Here, we report a case series of three cases of CA prostate with metastatic involvement of scrotal organs. All three patients had metastatic involvement of the spermatic cord, with involvement of epididymis in the first patient and testes in the third patient, revealed incidentally on orchiectomy. Two patients were also found to have coexisting lymphatic filariasis. To date as per the best of our knowledge, only one such case of CA prostate with metastasis to scrotal organs and associated filariasis has been reported. This highlights the need for histopathological evaluation of all orchiectomy specimens. Chronic infection and inflammation leading to lymphatic obstruction due to filariasis probably led to the unusual retrograde spread of the tumor.

A STUDY ON CORRELATION OF SERUM PROSTATE SPECIFIC ANTIGEN WITH CLINICAL AND PATHOLOGICAL VARIABLES IN PATIENTS OF PROSTATOMEGALY

Background: In clinical practice, biopsies are generally performed only when the results ofprostate specific antigen (PSA) test or digital rectal examination (DRE) are abnormal. This leads to misdiagnosis of most small prostatic cancers present in many older men. Patients with lower urinary tract infection (LUTS) who have serum PSA levels higher than 4ng/ml are primarily advised to undergo prostate biopsy to rule out cancer. However, PSA is organ specific not disease specific, so the presence of other prostate diseases such as benign prostatic hyperplasia (BPH) and prostatitis may influence its effectiveness for cancer detection. Hence, the PSA based prostate cancer detection is fraught with high false positive rate. Aim:To evaluate the utility of PSA assay as a method of investigation in diagnosis of prostatic lesion. Objectives: The use of Serum PSA levels for the early detection of prostate cancer and evaluate its role with other modalities for diagnosis of prostate cancer and to diagnose different diseases of prostate, i.e. prostatitis, BPH in prostatomegaly, and its correlation with Serum PSA levels. Materials and Methods: This prospective descriptive study was conducted in Index Medical College, Hospital & Research Centre, Indore, M.P,India in the period of August 2019 to July 2021. The patients were selected from the outdoor Department of General Surgery. Results: A total of 80 male patients presenting with LUTS were included. Their mean age was 68.66 years. The majority i.e. 41 of the study group were in the age group of 61-70 years. 42 of patients had Serum PSA < 4ng/ml. Biopsy proven adenocarcinoma cases 34% of the cases are in the age group of 61-70 years. Out of the biopsy proven adenocarcinoma cases, DRE was suspicious of malignancy in 89%. Conclusion: Serum PSA levels have a significant correlation with the age group, with the increase in age there is rise in Serum PSA levels. Transabdominal ultrasound, DRE and Serum PSA has high sensitivity in diagnosis of prostatomegaly but it was found that none of the screening tool has got much efficacy in differentiating carcinoma prostate from benign hypertrophy, but the combination of DRE and Serum total PSA or DRE, Serum total PSA and ultrasound abdomen showed higher efficacy in diagnosis of carcinoma prostate. Increase in Serum PSA is directly related to carcinoma, but there is no absolute cut-off for Serum PSAfor diagnosis of carcinoma. Key-Words: Prostate specific antigen, Prostatomegaly, Benign Prostatic Hypertrophy, Digital Rectal Examination, International Prostate Severity Score, Carcinoma Prostate.

Review: Veratrum californicum Alkaloids

Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17–45 Veratrum spp., Veratrum californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. californicum root and rhizome via liquid chromatography–mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.

Metastatic Adenocarcinoma of Prostate posing as upper tract ureteral mass

Prostate cancer metastasis to the ureter is extremely rare because only 45 such cases have been reported worldwide in the last century. It accounts for 30% of ureteral metastasis. Neuroendocrine differentiation is approximately 1% of the entire primary prostate adenocarcinoma pathology. Metastatic prostate cancer may pose as upper tract urothelial carcinoma. Prostate may look normal on clinic-radiological examination in prostate cancer. Majority of such cases are managed with nephroureterectomy. Herein, we report a case of 62-year gentleman, who presented with refractory left flank pain with repeated imaging suggestive of neoplastic left ureteric stricture and normal prostate on clinic-radiological examinations. The case was later found with the diagnosis of metastatic prostate adenocarcinoma with neuroendocrine differentiation after left sided nephroureterectomy done for a provisional diagnosis of Upper Tract Urothelial Carcinoma (UTUC).

Interaction of microRNAs with sphingosine kinases, sphingosine-1 phosphate, and sphingosine-1 phosphate receptors in cancer

Sphingosine-1-phosphate (S1P), a pleiotropic lipid mediator, participates in various cellular processes during tumorigenesis, including cell proliferation, survival, drug resistance, metastasis, and angiogenesis. S1P is formed by two sphingosine kinases (SphKs), SphK1 and SphK2. The intracellularly produced S1P is delivered to the extracellular space by ATP-binding cassette (ABC) transporters and spinster homolog 2 (SPNS2), where it binds to five transmembrane G protein-coupled receptors to mediate its oncogenic functions (S1PR1-S1PR5). MicroRNAs (miRNAs) are small non-coding RNAs, 21–25 nucleotides in length, that play numerous crucial roles in cancer, such as tumor initiation, progression, apoptosis, metastasis, and angiogenesis via binding to the 3′‐untranslated region (3′‐UTR) of the target mRNA. There is growing evidence that various miRNAs modulate tumorigenesis by regulating the expression of SphKs, and S1P receptors. We have reviewed various roles of miRNAs, SphKs, S1P, and S1P receptors (S1PRs) in malignancies and how notable miRNAs like miR-101, miR-125b, miR-128, and miR-506, miR-1246, miR-21, miR-126, miR499a, miR20a-5p, miR-140-5p, miR-224, miR-137, miR-183-5p, miR-194, miR181b, miR136, and miR-675-3p, modulate S1P signaling. These tumorigenesis modulating miRNAs are involved in different cancers including breast, gastric, hepatocellular carcinoma, prostate, colorectal, cervical, ovarian, and lung cancer via cell proliferation, invasion, angiogenesis, apoptosis, metastasis, immune evasion, chemoresistance, and chemosensitivity. Therefore, understanding the interaction of SphKs, S1P, and S1P receptors with miRNAs in human malignancies will lead to better insights for miRNA-based cancer therapy.