Madhu Mati Goel

Polymerase Chain Reaction vs. Conventional Diagnosis in Fine Needle Aspirates of Tuberculous Lymph Nodes

OBJECTIVE To compare four conventional methods of diagnosing tuberculous lymphadenophathy (TL)--namely fine needle aspiration cytology (FNAC), Zeihl-Neelsen staining of smears for acid-fast bacilli (AFB), culture for Mycobacterium tuberculosis (MTB) and lymph node biopsies--with the polymerase chain reaction (PCR) in order to assess the practicability and advantage of its use in routine diagnosis in a developing country. STUDY DESIGN Fine needle aspirates from 142 consecutive patients presenting with lymphadenopathy (mainly cervical) without any known systemic involvement underwent cytomorphologic diagnosis, AFB smears, culture for MTB, confirmatory biopsy and PCR for MTB. The aspirates from cases other than TL served as controls for PCR. RESULTS Correct diagnosis of tuberculosis could be made in 94.87% of cases by a combination of the four methods. PCR was done in 52 cases, 39 confirmed TL and 13 controls. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value of PCR were 94.44%, 38.23%, 44.73% and 92.85%, respectively, when culture alone was considered the gold standard. However, specificity (38.23-92.30%) and PPV (44.73-97.36%) of PCR increased remarkably when response to treatment was taken as the final arbiter. CONCLUSION The four conventional tests were found to be the methods of choice for the diagnosis of TL in developing countries. PCR should be reserved for problem cases.

PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

Abnormalities in ovarian function, including defective oogenesis and folliculogenesis, represent a key female reproductive deficiency. Accumulating evidence in the literature has shown that the PI3K/PTEN/Akt and TSC/mTOR signaling pathways are critical regulators of ovarian function including quiescence, activation, and survival of primordial follicles, granulosa cell proliferation and differentiation, and meiotic maturation of oocytes. Dysregulation of these signaling pathways may contribute to infertility caused by impaired follicular development, intrafollicular oocyte development, and ovulation. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/Akt and TSC/mTOR pathways during mammalian oogenesis and folliculogenesis and their association with female infertility.

Diagnostic Role of Survivin in Urinary Bladder Cancer

BACKGROUND Early diagnosis of carcinoma of bladder remains a challenge. Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is frequently activated in bladder carcinoma. The objective of this study was to investigate urinary survivin as a marker for diagnosis of urinary bladder. MATERIALS AND METHODS We examined urinary survivin concentration in 28 healthy individuals, 46 positive controls and 117 cases of histologically proven TCC prior to transurethral resection, using ELISA, and compared values with findings for urinary cytology. RESULTS Survivin was found to be significantly higher in the cancer group (P<0.05). A cut off value of 17.7 pg/ml was proposed, with an approximate sensitivity of 82.9% and specificity of 81.1% (P<0.0001), whereas urine cytology had a sensitivity of 66.7% and a specificity of 96.0%. CONCLUSIONS Urinary survivin can be used as a non-invasive diagnostic biomarker for TCC bladder, both for primary and recurrent disease.

Predictive Value of Fine Needle Aspiration Cytology of Bone Lesions

OBJECTIVE To determine the predictive value of fine needle aspiration cytology (FNAC) of bone lesions. STUDY DESIGN The study consisted of data retrieval on 200 cases of bone lesions and their cytohistopathologic correlation to assess the diagnostic efficacy of FNAC in these cases, considering histopathology as the gold standard. The diagnostic indices were calculated by a decision matrix comparison. RESULTS On cytohistopathologic correlation of 200 cases, 106 (53.0%) were malignant bone tumors (MBT): 97 primary and 9 metastatic; and 76 were benign bone lesions (BBL), 58 neoplastic (29%) and 18 nonneoplastic (9%). The aspirated material was adequate in 181 cases, whereas in 18 cases cytohistopathologic examination revealed no bony lesion. Thus, there were 163 evaluable cases, of which the specific morphologic diagnoses on FNAC were possible in 141 cases (86.5%), with a solitary false positive and 8 false negatives. The percentage of inadequate aspirates was more with BBL (13.2%) than MBT (8.5%). The overall diagnostic accuracy and sensitivity of bone lesions were 95.0%, whereas specificity, positive predictive value (PPV) and negative predictive value (NPV) were 94.7%, 99.4% and 69.2%, respectively. The sensitivity of FNAC was better (95.8%) with MBT as compared to BBL (91.7%), whereas specificity and PPV were almost equal (98.8% and 99.2%) in both cases. The NPV in cases of BBL was higher (97.8%) than in MBT (95.2%). These diagnostic indices were calculated excluding the inadequate cases. CONCLUSION High PPV and NPV indicate the reliability of FNAC for the diagnosis of bone lesions.

Significance of obesity markers and adipocytokines in high grade and high stage prostate cancer in North Indian men – A cross-sectional study

BACKGROUND Prostate cancer (CaP) in India is the 10th most common malignancy affecting men. CaP incidence in India is low, but rising like other countries. The reasons for this racial disparity are uncertain. The foremost reasons that may underlie regional/ethnic differences are genetic polymorphisms, altered hormonal status, socioeconomic status, and obesity. This study aimed at investigating the role of adipocytokines in stimulating the promotion and progression of CaP. METHODS A cross-sectional study on histopathologically proven prostate cancer (N=95) and benign prostatic hyperplasia (N=95) patients was undertaken. CaP patients were classified into high-grade (N=62) and low-grade (N=33), and high stage (N=31) and low stage (N=64) groups. The level of body mass index (BMI), waste to hip ratio (WHR), interleukin-6 (IL-6), leptin, and adiponectin were compared between BPH and CaP groups and between grades and stages of prostate cancer. RESULTS The level of BMI was significantly (p<0.001) higher in CaP patients (26.58±4.76) in comparison to BPH (22.15±2.90). Similarly, WHR was significantly (p<0.0001) higher in the CaP patients (1.08±0.37) in comparison to BPH (0.86±0.15). Leptin (BPH: 25.60, CaP: 56.00) and II-6 levels (BPH: 9.90, CaP: 32.30) were significantly higher, but adiponectin was significantly lower in CaP patients as compared to BPH. High grade CaP patients had significantly higher BMI and WHR in comparison to low grade, and WHR was also higher in high stage CaP. Leptin and IL-6 level were higher in high stage and high grade, but adiponectin was low in high stage and high grade groups in comparison to low stage and low grade groups. CONCLUSIONS Higher BMI and WHR correlate with prostate cancer independently, suggesting obesity to be a promoter of poor prostate health. Leptin and IL-6 appear to have stimulating effect on prostate cancer cells inducing the promotion and progression of CaP, but adiponectin appears to be protective against prostate cancer.

Primary Rosai-Dorfman disease of bone without lymphadenopathy diagnosed by fine needle aspiration cytology. A case report.

BACKGROUND Solitary bone involvement without lymphadenopathy is a rare manifestation of Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy (SHML). Only 11 cases have been reported in the literature to date, all diagnosed on histology. CASE A 7-year-old girl had a radiolucent, lytic lesion in the shaft of the tibia clinically simulating Ewings sarcoma. Fine needle aspiration cytology (FNAC) showed a microscopic picture typical--of SHML. There was no lymphadenopathy. CONCLUSION Rosai-Dorfman disease sometimes involves bone without lymphadenopathy and can be diagnosed confidently on FNAC. To the best of our knowledge, this is the 12th case report of solitary bone involvement.

VEGF-A immunohistochemical and mRNA expression in tissues and its serum levels in potentially malignant oral lesions and oral squamous cell carcinomas

The aim of the study was to investigate whether the estimation of circulating Vascular endothelial growth factor-A (VEGF-A) levels by ELISA could be used as surrogate of VEGF-A expression in tissues of pre-malignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC) as compared to that in healthy controls. The study samples comprised of tissue and blood samples from 60 PMOLs, 60 OSCC, and 20 healthy controls. Serum VEGF-A levels were determined by an ELISA based assay (Quantikine human VEGF; R & D System, Minneapolis USA). Tissue VEGF-A expression and microvessel density (MVD) were assessed by immunohistochemistry (IHC) using antibodies against VEGF-A and CD-34 on formalin fixed paraffin embedded (FFPE) tissue sections. VEGF-A mRNA expression was analyzed by real-time PCR in snap frozen tissues. Serum VEGF-A levels and immunohistochemical VEGF-A expression were significantly high in PMOLs and OSCC in comparison with controls. VEGF mRNA gene expression showed more than 50-fold increase in PMOLs and OSCC. VEGF-A levels in serum correlated in a linear fashion with the tissue expression in oral pre-malignant and malignant lesions, suggesting that the serum levels may serve as surrogate material for tissue expression of VEGF-A.

Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70-80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial-mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis - the most fatal consequence of endometrial carcinogenesis.

Expression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) in human urinary bladder transitional cell carcinoma.

The objective of this study was to evaluate the expression pattern of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) and its clinical significance in human bladder cancer (BC). We detected PBK/TOPK mRNA overexpression in BC and human normal testis tissues using RT-PCR. Using qRT-PCR revealed a higher expression of PBK/TOPK in BC tissues than their adjacent noncancerous tissues (ANCTs) (p<0.0001). Cytoplasmic expression of PBK/TOPK protein was found to be positive in 64.6% (42 of 65) BC patients. Expression of PBK/TOPK protein was found to be significantly higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC) (86.1% vs. 37.9%, p<0.001). The immunohistochemical (IHC) expression of PBK/TOPK was found to be significantly (p<0.001) associated with the stage of disease. Study findings suggest that the PBK/TOPK mRNA/protein expression is specific to human BC and might be used as a novel target for development of cancer immunotherapy and diagnostic biomarker.

Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study

Introduction TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear. Methods We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA. Results c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p = 0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p<0.001). Conclusion c.29C>T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations.