[Show abstract][Hide abstract] ABSTRACT: Background:
The microseminoprotein gene encoding prostate secretory protein of 94 amino acids (PSP94) harbours a potential risk allele (rs10993994) for prostate cancer (PCa) in its promoter region. However, studies on rs10993994 have been sparse in Asian Indians.
The present study recruited a sample population of 44 benign prostatic hyperplasia patients, 33 PCa patients and 60 healthy participants, of which, participants without other confounding risk factors for PCa were retained. The serum PSP94 (sPSP94) levels were measured by a serum-based ELISA in an earlier study. A novel RFLP technique was developed to screen for rs10993994 which was validated with direct sequencing.
Sequencing showed additional 4 SNPs (rs41274660, rs141211965, rs12770171, rs10669586) and 2 novel variants (GenBank accession nos. KM265191 and KM265192). In silico DNA topographical studies predicted that KM265192 would have higher cleavage intensity and more accessibility for binding of transcription factors. Even though, similar frequencies were observed for all the variants in all the three study groups, the risk allele 'T' (rs10993994) was seen to be associated with reduced PSP94 expression both at mRNA and protein level. Further, mRNA expression as studied by real-time PCR correlated positively with sPSP94 levels. Interestingly, CC genotype of rs10993994 showed highest sPSP94 levels in all the three study groups and was associated with Gleason score ≤7 in PCa patients. In contrast, TT genotype of rs10993994 was associated with lesser sPSP94 levels and with aggressiveness of PCa.
rs10993994 was found to be a functional SNP in the studied Asian Indian population.
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) is the main causative agent for cervical cancer. Variability in host immunogenetic factors is important in determining the overall cellular immune response to the HPV infection. This study was carried out to confirm the association between human leukocyte antigen (HLA) class II alleles and cervical cancer in HPV infected women.
b0 oth low and high resolution methods were used to genotype HLA class II (DRB1 and DQB1) alleles in 75 women with cervical cancer (cases) and 75 HPV positive women and 100 HPV negative women with healthy cervix (controls). odds ratio and 95% confidence interval were calculated. Co-occurring HLA alleles (haplotype) across cases and controls were also studied.
Significant association was found for HLA-DRB1FNx0103(FNx0113:01) and - DQB1FNx0102(FNx0102:01) with increased risk for cervical cancer. Also, HLA-DRB1FNx0113(FNx0113:01); -DQB1FNx0106 and -DQB1FNx0103:02 were significantly associated with decreased risk for cervical cancer. Haplotype analysis highlighted the significant association of HLA- DRB1FNx0107:01-DQB1FNx0102:02 and HLA DRB1FNx0110:01-DQB1FNx0105:01 with cervical cancer, while HLA-DRB1FNx0114:04-DQB1FNx0105:03 and DRB1FNx0115:01-DQB1FNx0106:01 conferred decreased risk for cervical cancer. Multivariate analysis highlighted the association of specific alleles with cervical cancer after adjusting for confounding factor age.
There were possible associations of specific HLA class II alleles either with risk of developing cervical cancer, or with its protection. Our results confirmed the assessment of DRB1FNx0113 as a protective marker in HPV infection outcome. our study also revealed protective association of homozygous haplotype DRB1FNx0115- DQB1FNx0106 with cervical cancer.
No preview · Article · Nov 2014 · The Indian Journal of Medical Research
[Show abstract][Hide abstract] ABSTRACT: We studied the relationship between human leukocyte antigen (HLA) class I alleles and cervical cancer among Indian women. Seventy-five cervical cancer cases were compared with 175 noncancer controls. Cervical biopsy tissue specimen from cancer cases and cervical swab specimen from controls were collected for HPV detection and typing. Blood was taken for HLA typing by PCR-SSOP method. The impact of HLA class I alleles on cervical cancer risk was evaluated using StatCalc program (Epi Info version 6.0.4. CDC Atlanta, GA, USA), and confirmed with Bonferroni correction. Results revealed HLA-B*37, HLA-B*58 were associated significantly with increased risk while HLA-B*40 with decreased risk for cervical cancer. At high-resolution analysis after Bonferroni correction, HLA-B*37:01 allele was associated with increased risk, whereas HLA-B*40:06 was with decreased risk for cervical cancer. HLA-B*37:01 and HLA-B*40:06 belong to the same superfamily of HLA-B44. In silico analysis revealed different binding affinities of HLA-B*37:01 and HLA-B*40:06 for the epitopes predicted for E6 and L1 proteins of HPV16. The higher binding affinity of epitopes to B*40:06, as revealed by docking studies, supports the hypothesis that this allele is able to present the antigenic peptides more efficiently than B*37:01 and thereby can protect the carriers from the risk of cervical cancer. Thus, there is a clear indication that HLA plays an important role in the development of cervical cancer in HPV-infected women. Identification of these factors in high-risk HPV-infected women may help in reducing the cervical cancer burden in India.
[Show abstract][Hide abstract] ABSTRACT: Background:
The serum PSA (sPSA) test has low specificity for prostate cancer (PCa), since sPSA also rises in benign prostatic hyperplasia (BPH). Serum PSP94 (sPSP94), a major secreted prostate protein, is indicated as a PCa marker. The potential of sPSP94 and sPSA in conjunction with each other to improve specificity of diagnostic test for PCa needs to be evaluated.
PCa patients (n=33), BPH patients (n=44) and healthy controls (n=50) were recruited. A serum-based sandwich ELISA was developed to measure sPSP94 concentrations. Utility of sPSP94 in improving specificity of sPSA test was evaluated by studying sPSP94/sPSA ratios of study participants.
Considerable decrease in overlap among sPSP94/sPSA ratio values of BPH and PCa patients was observed, as compared to sPSP94 or sPSA alone. For differentiating between BPH and PCa patients, this ratio had a maximum area under the curve (AUC) of 0.859 (P=0.0132) and had a comparable sensitivity (90.91%) to sPSA with an increased specificity of 70.45%. Further, decision curve analysis (DCA) showed that sPSP94/sPSA ratio had a superior net benefit in identifying PCa, in patients opting for biopsy.
The sPSP94/sPSA ratio can be a better differentiating marker between BPH and PCa, than sPSP94 or sPSA alone.
Full-text · Article · Jun 2014 · Clinica Chimica Acta
[Show abstract][Hide abstract] ABSTRACT: Background:
Paraganglioma (PG) of the urinary bladder is a rare neuroendocrine neoplasm, accounting for < 0.1% of all bladder tumours. Distinction from urothelial carcinoma is imperative as management and prognosis vary markedly. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder.
Materials and methods:
All cases of PG of urinary bladder diagnosed at our institute from 2002-2012 were retrieved and diagnosis confirmed in accordance with WHO classification. Clinical and treatment details were obtained from hospital medical records.
Fourteen cases of PG of urinary bladder including 5 consult cases were analysed. These included 11 transurethral resections ± partial cystectomies, 2 partial cystectomies and 1 radical cystectomy. Two out of the 5 consult cases had been submitted with a diagnosis of urothelial carcinoma and 1 with that of a rhabdomyosarcoma. Age ranged from 15-84 years (median, 43 years) with a male to female ratio of 1:2.5. Presenting symptoms were haematuria, dysuria and flank pain; only 1 case had antecedent hypertension. Histologically, typical 'zellballen' (72%), diffuse (21%) and ribbon-like (7%) growth patterns amidst a richly vascularised stroma were seen. Muscularis propria invasion and necrosis was present in 72% and 21%, respectively. Substantial cautery artifacts led to misdiagnosis in the 3 erroneous cases. Tumour cells were positive for chromogranin, synaptophysin; sustentacular cells were S-100 positive. Follow up was available in 6 patients; median follow-up was 29 months (8-120 months). One patient developed distant metastasis in cervical lymph node 10 years after diagnosis; remaining were alive without evidence of disease.
Paraganglioma of the urinary bladder is a rare tumor and may be misdiagnosed as urothelial cancer especially on TURBT, but a high index of suspicion, careful search for the characteristic histological features and supportive immunohistochemical studies should lead to a correct diagnosis.
No preview · Article · Apr 2014 · Indian Journal of Pathology and Microbiology
[Show abstract][Hide abstract] ABSTRACT: Introduction:
A retrospective review in patients with carcinoma cervix to evaluate the changes and trends in demographics, evolution of protocols, and outcome analysis over 16 years.
Materials and methods:
This is a retrospective study of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and 1994. All the work-up, staging investigations, treatment details, radiation protocols, outcomes, and toxicities were noted, compiled, and analyzed.
With a mean age of 46 years (range: 18-90 years; median: 45 years), 669 (11%) patients were in stage Ib, 284 (5%) were in stage IIa, 1891 (30%) were in stage IIb, 69 (1%) were in stage IIIa, and 3321 (53%) were in stage IIIb. With a median follow-up of 68 months (57-79 months) for the entire group, there was no significant difference in the outcome of 953 patients with international federation of gynecology and obstetrics (FIGO) Ib-IIa treated after radical surgery, pre-operative radiation therapy (pre-op RT) + Sx or after radical radiation; their disease-free survival (DFS) was 60-62% at 8 years. In our series of 1891 patients with stage IIb and 3321 with stage IIIb, a respective DFS of 56% and 40% was achieved at 8 years.
Over the last two decades, with the acquisition of newer facilities and inception of Joint Clinics, there has been a significant refinement in the treatment protocols and outcome. Improving radiation strategies to improve therapeutic ratio is the key to success.
No preview · Article · Oct 2013 · Journal of cancer research and therapeutics
[Show abstract][Hide abstract] ABSTRACT: Aims and objectives:
To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors associated with treatment outcome and survival.
Materials and methods:
The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up.
A total of 27 cases of primary ovarian carcinosarcoma were identified. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV) at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component) and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months). The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT.
Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.
No preview · Article · Oct 2013 · Indian Journal of Pathology and Microbiology
[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) in the CTLA-4 gene exert differential effects on T-cell response to viral infection. We aimed to evaluate the association of two SNPs of the CTLA-4 gene with cervical cancer in Indian women. The two polymorphic loci, one in the promoter region -318 C>T, rs5742909 (100 cervical cancer cases and 101 controls) and the other in exon 1 +49 A>G, rs231775 [104 cervical cancer cases and 162 controls] were genotyped using polymerase chain reaction-restriction fragment length polymorphism methods. Haplotype block structure was determined using Haploview 4.2. The statistical analyses were performed using a commercially available statistical software package, whereas PyPop was used to calculate the haplotypic frequencies. In this case-control study, the A/A genotype frequency (30.76% vs. 17.6%, P = 0.01) as well as the allelic frequency for A (52.8% vs. 43.5%, P = 0.04) was significantly higher in cases compared to controls. No significant association was seen in the -318 C>T polymorphism. In forward stepwise binary logistic regression analysis considering age and parity as potential confounders, significant association was demonstrated between +49 A/A and cervical cancer. Most likely, this is the first study from India to highlight the significant association between the CTLA-4 gene +49 A/A SNP and cervical cancer, thus adding to the global knowledge of the association of this SNP with cervical cancer.
[Show abstract][Hide abstract] ABSTRACT: Carcinoma penis is one of the common malignancies in developing world especially among rural population. Multimodality treatment with surgery, radiation and chemotherapy for advanced penile carcinoma with groin nodal metastasis is crucial to optimise the outcome. Cisplatin, fluorouracil, methotrexate, vinorelbine, bleomycin and paclitaxel are the common chemotherapeutic agents used along with local therapy. Paucity of data to show superiority of one chemotherapeutic regime over another and only modest response to any combination chemotherapy. Progression of disease after surgery, radiation and chemotherapy is associated with poor outcome and quality of life. Nimotuzumab, Anti EGFR monoclonal antibody, along with paclitaxel in our case of resistant metastatic penile carcinoma has shown good symptomatic palliation and clinical response.
No preview · Article · Apr 2013 · Indian journal of medical and paediatric oncology
[Show abstract][Hide abstract] ABSTRACT: To study the efficacy and safety of paclitaxel and platinum doublet chemotherapy in penile cancer patients with high-risk features of local failure.
Retrospective analysis was done of patients with 19 carcinoma of the penis who were offered adjuvant chemotherapy with paclitaxel and platinum combination. The data regarding the surgical details, high-risk features for which chemotherapy was offered, chemotherapy toxicity details (in accordance with CTCAE vs 3), failure pattern, and survival data were noted. SPSS version 16 was used for statistical analysis. Descriptive and Kaplan-Meier survival analysis was performed.
Median age of patients was 48 years. Fifteen patients received paclitaxel in combination with cisplatin and four received paclitaxel with carboplatin in view of their low serum creatinine clearance. The treatment was completed by 12 patients (63.2%). Of 79 planned cycles, 50 were taken. The treatment was well tolerated with grade 3-4 gastrointestinal toxicity was seen in 1 patient, grade 3 neurological toxicity in one and grade 5 neutropenia in one patient. Treatment related death occured in one patient. The median follow-up was 15.33 months and 6 loco-regional relapsed had taken place. The estimated median DFS was 16.2 months and the estimated median OS was not reached. The estimated DFS for treatment completed patients was 23.13 months as against 2.16 months for patients not completing treatment.
The platinum and taxane doublet chemotherapy was found to be safe and effective.
[Show abstract][Hide abstract] ABSTRACT: The present study describes the clinicopathologic analysis of 34 cases of Ewing sarcoma/primitive neuroectodermal tumor occurring in the kidney. The patients were 21 males and 13 females with an age range of 6 to 44 years. Clinically, patients presented with multiple symptoms including hematuria, pain, and/or lump in the abdomen. Nephrectomy was performed in most of the cases. Grossly, whole of the renal parenchyma was involved by a variegated tumor. Histologically, the tumor was composed of monomorphic, small, and round cells arranged in a variety of patterns. Rosettes, geographical areas of necrosis, and arborizing vascular pattern were the prominent histologic features. The nucleus was monomorphic and round. Anisonucleosis was also noted in some cases. The nucleus was mostly hyperchromatic. A mixture of hyperchromatic and powdery chromatin was noted in few cases. Immunohistochemically, MIC2 (CD99) was positive in 32 of 34 cases followed by neuron-specific enolase (9/12 cases), vimentin (8/14 cases), synaptophysin (1/8 cases), and S-100 protein (1/4 cases). Molecular analysis by reverse transcriptase-polymerase chain reaction that was carried out in 26 cases revealed presence of EWS-FLI-1 type 1 translocation in 12 cases, EWS-FLI-1 type 2 translocation in 10 cases, and both type 1 and type 2 EWS-FLI-1 translocation in 2 cases. Two cases did not demonstrate any translocation. Follow-up data were available for 17 of 34 cases. Local recurrence of the tumor was seen in 4 patients, and 10 patients were recorded to have distant metastasis in various organs, such as lung, bone, and lymph node, during the course of the disease.
No preview · Article · Apr 2012 · Annals of diagnostic pathology
[Show abstract][Hide abstract] ABSTRACT: Neuroendocrine carcinomas of the cervix are uncommon, characterized by a histomorphological spectrum and, mostly, an aggressive clinical course. There are only few substantial studies on such cases documented from our country, where cervical cancer is the second most common cancer affecting women. Herein, we present a spectrum of 50 cervical neuroendocrine carcinomas, including histopathologic features, terminology, immunohistochemical (IHC) profile, and clinical outcomes, wherever available. Fifty tumors occurred in women, with their age ranging from 23 to 69 years (mean, 48.6 years; median, 46.5 years). Stagewise, among 25 cases, most cases (6, or 24%) presented with stage IB. Average tumor size was 4.7 cm. On histopathologic review, 26 tumors (52%) were classified as small cell carcinoma (SMCA); 14 (28%), as large cell neuroendocrine carcinomas (LCNECs); 4 (8%), as SMCA+LCNECs; and 6, as mixed carcinomas, including 3 tumors (6%) with SMCA and squamous cell carcinoma (SCC), 2 tumors (4%) with LCNEC and adenocarcinoma, and a single tumor (2%) with LCNEC and squamous cell carcinoma. On IHC performed in 41 tumors (82%), 36 tumors (87.8%) were positive for at least a single neuroendocrine marker, and 22 (53.6%) expressed 2 neuroendocrine markers. Synaptophysin was positive in 22 (59.4%) of 37 tumors; chromogranin, in 27 (72.9%) of 37; CD56, in 8 (100%) of 8; and neuron-specific enolase in 7 (87.5%) of 8 tumors. Treatment wise, among 30 patients (60%), 6 (20%) underwent surgery, including Wertheim hysterectomy (5) and simple hysterectomy (1); 8 (26.6%) underwent surgery with adjuvant treatment, and 10 patients (33.3%) were offered chemotherapy and/or radiotherapy. On follow-up (27 patients, or 54%) over 1 to 144 months, 16 patients (59.2%) were alive with disease over median duration of 9 months, and 7 (25.9%) were free of disease over median duration of 26.5 months. There were 5 recorded deaths. Thirteen tumors (48.1%) metastasized, most commonly to liver. In cases with early stage disease and adjuvant treatment, including radiotherapy, LCNEC histology fared well. This study forms the largest documented series on cervical neuroendocrine carcinomas from our country, testifying the current histopathologic classification system. Although SMCAs can be recognized on morphology, LCNECs need to be correctly identified because these can be misdiagnosed in the absence of neuroendocrine markers. Synaptophysin, chromogranin, and CD56 are optimal IHC markers. Small cell carcinomas, pure or mixed, are relatively more aggressive. All these tumors are best treated with multimodal therapy. Early stage disease treated with radical surgery and adjuvant treatment seems to increase survival. Despite aggressive treatment, prognosis is dismal.
[Show abstract][Hide abstract] ABSTRACT: With an aim to analyze and document the outcome of Stage I Seminoma patients we undertook a retrospective analysis of patients treated between January 1990 and December 1998. The treatment charts of patients treated between January 1990 and December 1998 were reviewed. Patient and tumor characteristics, treatment details, relapse rates, late toxicities, or occurrence of second primary was noted. Royal Marsden Staging System was utilized because of its simplicity and wide-use in the above period. Out of 137 patients, 41 (30%) patients did not receive any further treatment, 96 (70%) patients received prophylactic radiotherapy to para-aortic and pelvic nodes. The observation group patients had a median follow-up 20 months, 9 patients had nodal relapse with 7 in retroperitoneal nodes and 2 patients in inguinal nodes. Of these, 7 patients received BEP chemotherapy and 2 patients Chemoradiation. Four patients had complete remission while remaining 5 patients had partial response. The histopathologies of all the 5 patients with partial response were reviewed to reconfirm the diagnosis. Patients of prophylactic radiotherapy group had a follow-up of 33 months, 6 patients relapsed, RP nodal disease in 5 patients and distant metastasis in 1 patient. All these patients received BEP chemotherapy. One had complete response and remaining 5 patients had partial response. The group of patients under observation had a significantly higher relapse rate and lower disease free compared to the adjuvant radiotherapy group (73.5% vs. 91% at five years, p value 0.004). Disease specific survivals for the two groups were however similar (89% vs. 93%) at five years, p value 0.18). We conclude that Stage I Seminoma patients treated with prophylactic radiation to paraaortic and pelvic region had better outcome. Key words: Seminoma, Observation, Adjuvant Radiotherapy.
No preview · Article · Jan 2012 · gulf journal of oncology, The
[Show abstract][Hide abstract] ABSTRACT: To study the histological features in uterine STUMP, and atypical leiomyomas (AL), and to correlate with clinical outcome.
From January 2004 to August 2010, a total of 21 cases were retrieved from records, labeled as STUMP(7), AL (5), AL with low risk of recurrence (2), smooth muscle tumor of low malignant potential (STLMP) (2), and symplastic leiomyoma (5). The slides were reviewed for coagulative tumor cell necrosis (CTCN), hyaline necrosis/ infarction type necrosis, presence and degree of cytological atypia, mitotic activity, epithelioid morphology and myxoid features. The other characteristics (such as size, circumscription, individual tumor cell necrosis), were noted, wherever available.
The mean age was 45 years (median 46; range 24-67 yrs). CTCN was seen in 2 cases on examination of additional material; wherein a revised diagnosis of leiomyosarcoma had been given. Infarction type necrosis and individual cell necrosis was seen in 2 and 3 cases, respectively. Mitoses were less than 5/10 hpf in all the cases. One of the tumours labeled as STUMP also had concurrent endometrial adenocarcinoma. Follow up: Follow-up was available in 11 cases (52.3%). One patient had died. (cause not known). In 10 patients, the follow-up ranged from 4 to 56 months (mean 20.9 months; median 15 months) nine patients were alive and well. One patient (labeled STLMP) had metastatic liver disease 3 yrs after the primary surgery, at the last follow-up.
1) There is an overlap in using the terminologies as STUMP, AL, AL with low risk of recurrence, AL with low malignant potential. A designation of STUMP does convey a category of borderline malignancy to the gynecological surgeons. Most behave in a benign fashion and follow-up without adjuvant therapy is currently recommended. Critical evaluation of coagulative tumor necrosis is essential. Follow-up remains a challenge in our setting.
No preview · Article · Oct 2011 · Indian Journal of Pathology and Microbiology
[Show abstract][Hide abstract] ABSTRACT: This study assessed the potential of tomotherapy based Image Guided Radiotherapy (IGRT) to increase the accuracy of bladder irradiation using a 'plan of the day' adaptive radiotherapy (ART) technique.
Ten patients with muscle invasive bladder cancer underwent bladder preservation with trimodality therapy in an ongoing trial. All patients received 64 Gy/32# to the whole bladder and seven of them received a boost of 68 Gy/32# to the tumour bed. The ART technique entailed the generation of six IMRT plans for each patient, using six isotropic PTVs of 5-30 mm applied to the bladder volume (CTV) to generate the PTVs. Megavoltage CT (MVCT) imaging was done to correct positioning errors and choose the 'plan of the day'.
Post treatment MVCT scans (315 scans) were used to generate multiple anisotropic PTVs for three hypothetical scenarios. Overall, coverage of anterior and superior walls required larger margins than other walls. Maximum geographical miss, in spite of IGRT, was noted for the superior (13.8%) and anterior walls (10.3%).
Plan of the day ART is a feasible and promising technique for optimal treatment and dose escalation in bladder cancer.
No preview · Article · Mar 2011 · Radiotherapy and Oncology