S. V. S. Deo

Identification of differentially expressed genes in oral squamous cell carcinoma.

Rapid advances in multimodality therapy have not significantly improved the overall 5‐yr survival of oral cancer patients in the past two decades, thereby underscoring the need for molecular therapeutics. The development of new treatment strategies for more effective management of oral cancer requires identification of novel biological targets. Therefore, the aim of this study was to identify novel genes associated with oral tumorigenesis by comparing gene expression profile of oral squamous cell carcinomas (OSCCs) and matched nonmalignant oral epithelial tissues with differential display. Of the 180 differentially expressed cDNAs isolated, reamplified, and cloned into pGEMT‐Easy Vector, 26 cDNAs were confirmed to be upregulated in OSCCs by reverse Northern blot analysis. The differentially expressed genes included components of immune system, signaling pathways, angiogenesis, cell structure, proliferation, apoptosis, cell‐adhesion, and cellular metabolism. Reverse transcription (RT)‐polymerase chain reaction (PCR) analysis of 15 OSCCs and matched nonmalignant oral tissues provided the first evidence that 14‐3‐3‐zeta, melanoma metastasizing clone D (MEMD), KIAA0471, sperm protein 17 (SP17), TC21, and anti‐TNF α antibody are upregulated in OSCCs. Immunohistochemical analysis confirmed overexpression of 14‐3‐3‐zeta and TC21 protein, a member of the Ras family, in OSCCs as compared to histologically normal oral tissues validating the differential display analysis. Identification of six novel differentially expressed genes in oral tumors adds to the repertoire of genes associated with oral carcinogenesis and provides candidate potential biological targets for diagnosis and/or therapy. Further characterization of the 14 unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying oral tumorigenesis.

MEMD/ALCAM: A Potential Marker for Tumor Invasion and Nodal Metastasis in Esophageal Squamous Cell Carcinoma

Objective: TheMEMD gene was reported to be overexpressed in human esophageal squamous cell carcinoma (ESCC), using differential display. The aim of this study was to determine the clinical significance of MEMD/ALCAM in esophageal tumorigenesis. Methods: Analysis of MEMD/ALCAM expression in esophageal tissues was carried out at protein and RNA level using immunohistochemistry and semiquantitative RT-PCR, respectively. Results: Increased MEMD/ALCAM expression was observed in 42/65 (65%) ESCCs (p = 0.000, odds ratio, OR = 3.665) and in 17/25 (68%) dysplasias (p = 0.000, OR = 4.248) compared to paired distant histologically normal esophageal tissues. Increased MEMD mRNAlevels were observed in ESCCs and dysplasias showing overexpression of MEMD/ALCAM protein. Interestingly, increased membranous MEMD/ALCAM expression was observed in dysplasias in comparison with ESCCs (p = 0.002, OR = 3.177). MEMD/ALCAM overexpression in ESCCs was associated with late clinical stage (p = 0.002, OR = 3.619), enhanced tumor invasiveness (p = 0.002, OR = 3.619), and nodal metastasis (p = 0.000, OR = 4.206). Conclusion: To our knowledge, this is the first report showing MEMD expression at pre-malignant stage (dysplasia), suggesting that MEMD/ALCAM expression is an early event in the development of esophageal cancer. Furthermore, in ESCCs its correlation with late clinical stage, enhanced tumor invasiveness and nodal metastasis suggests an association with aggressive tumor behavior. Our data suggest that MEMD/ALCAM may serve as a potential marker for early diagnosis, tumor invasion and nodal metastasis in ESCCs.

Modified radical mastectomy using harmonic scalpel.

Modified radical mastectomy (MRM) remains the most commonly performed surgery for breast cancer today. Conventional surgery using scalpel and electrocautery is associated with moderate blood loss and morbidity in the form of haematoma, flap necrosis, prolonged axillary drainage, and seroma. This study was performed to evaluate the feasibility of using ultrasonic energy (harmonic scalpel) for MRM and to standardise the operative technique of harmonic scalpel MRM using various available accessories of the harmonic scalpel.

GSTP1 methylation and polymorphism increase the risk of breast cancer and the effects of diet and lifestyle in breast cancer patients

Glutathione S-transferases (GSTs) are an important group of isoenzymes that play an essential role in the detoxification of carcinogens. Polymorphism at exon 5 of the GST π family decreases the catalytic activity and affects the detoxification ability of the enzyme, GSTP1. GSTP1 promoter hypermethylation and loss of expression are frequently observed in various types of carcinoma. We hypothesized that somatic epigenetic modification in homozygous mutants increases the degree to which breast cancer risk is affected by lifestyle factors and dietary habits. The present study used tumor biopsies and blood samples from 215 breast cancer patients and 215 blood samples from healthy donors. GSTP1 polymorphism was studied using PCR-restriction fragment length polymorphism, methylation using methylation-specific PCR and loss of expression using immunohistochemistry and western blotting. No significant increase was observed in the breast cancer risk of individuals with the mutant (Val) allele [odds ratio (OR), 1.48; 95% confidence interval (CI), 0.97–2.26 for heterozygotes; OR, 1.42; 95% CI, 0.86–2.42 homozygous mutants]. GSTP1 promoter hypermethylation was detected in one-third of tumor biopsies (74/215) and was found to be associated with a loss of expression. Genotype and tumor methylation associations were not observed. Estrogen (ER) and progesterone (PR) receptor-positive tumors had a higher methylation frequency. GSTP1 polymorphism was not associated with increased promoter hypermethylation. The results suggest that GSTP1 methylation is a major event in breast carcinogenesis and may act as a tumor-specific biomarker.

Surgical management of skin cancers: Experience from a regional cancer centre in North India

AIMS To review the disease profile and treatment outcome of patients with primary skin malignancies treated at a regional cancer centre. SETTINGS AND DESIGN Surgical oncology unit of a tertiary care regional cancer centre. Evaluation of treatment outcome of patients with skin cancer from Surgical Oncology database was done. MATERIALS AND METHODS Retrospective analysis of records of 77 patients with skin cancers treated between 1995 and 2002 was conducted. Profile of patients with skin cancer, surgical details including the management of primary tumour, regional lymph nodes and reconstructive procedures performed and survivals were analysed. STATISTICAL ANALYSIS All computations were done using the Statistical Package for Social Sciences (SPSS-9). Descriptive statistics were calculated in a standard fashion and survival analysis was performed using Kaplan-Meier method. RESULTS Skin cancers constituted 2.4% (77/3154) of patients with cancer treated in the surgical oncology department. Squamous cell carcinoma (SCC) was the most common histological type (55.8%) followed by melanoma (26.1%) and basal cell carcinoma (BCC, 18.1%). Forty one percent of patients had undergone some form of intervention elsewhere before being referred. Reconstruction was required in 55.8% patients with large postresection defects. Regional lymph nodal dissection was required in 32.4% of total patients. Five-year median disease-free survival for the entire study population was 75%. CONCLUSIONS Skin cancers constitute a small but significant proportion of patients with cancer. Unlike in the Western countries, SCC is the commonest histologic variety. Primary level inadequate intervention is very common. Optimal results can be obtained with radical surgery and optimal surgical margins along with a reconstructive procedure when needed.

Clinico-pathological profile of lung cancer at AIIMS: a changing paradigm in India.

BACKGROUND Lung cancer is one of the commonest and most lethal cancers throughout the world. The epidemiological and pathological profile varies among different ethnicities and geographical regions. At present adenocarcinoma is the commonest histological subtype of non-small cell lung cancer (NSCLC) in most of the Western and Asian countries. However, in India squamous cell carcinoma has been reported as the commonest histological type in most of the series. The aim of the study was to analyze the current clinico-pathological profile and survival of lung cancer at our centre. MATERIALS AND METHODS We analyzed 434 pathologically confirmed lung cancer cases registered at our centre over a period of three years. They were evaluated for their clinical and pathological profiles, treatment received and outcome. The available histology slides were reviewed by an independent reviewer. RESULTS Median age was 55 years with a male:female ratio of 4.6:1. Some 68% of patients were smokers. There were 85.3% NSCLC and 14.7% SCLC cases. Among NSCLCs, adenocarcinoma was the commonest histological subtype after the pathology review. Among NSCLC, 56.8% cases were of stage IV while among SCLC 71.8% cases had extensive stage disease. Some 29% of patients could not receive any anticancer treatment. The median overall and progression free survivals of the patients who received treatment were 12.8 and 7.8 months for NSCLC and 9.1 and 6.8 months for SCLC. CONCLUSIONS This analysis suggests that adenocarcinoma may now be the commonest histological subtype also in India, provided a careful pathological review is done. Most of the patients present at advanced stage and outcome remains poor.

An Update in the Management of Malignant Pleural Effusion

Malignant pleural effusion (MPE) usually presents in the disseminated and advanced stage of malignancy. Dyspnea is the debilitating symptom which needs palliation in these patients. Various modalities are available in the management of MPE. Careful consideration of the patients expected survival and quality of life is needed when deciding the optimum treatment modality in such patients. In this article, different modalities of the palliative management of MPE are discussed with an attempt to derive a treatment algorithm for the management of MPE.

Genetic polymorphisms of ESR1, ESR2, CYP17A1, and CYP19A1 and the risk of breast cancer: a case control study from North India

Estrogen is a key driver of breast cancer and genes involved in its signaling and biosynthesis are crucial in breast cancer progression. In this study, we investigated the role of estrogen signaling and synthesis related genes polymorphism in susceptibility to breast cancer risk in North India population in a case–control approach. We examined the association of single nucleotide polymorphism (SNP) in estrogen receptors, ESR1 (rs2234693) and ESR2 (rs2987983); estrogen biosynthesis enzymes, CYP17A1 (rs743572); and aromatase, CYP19A1 (rs700519) with breast cancer risk. Cases (n = 360) were matched to controls (n = 360) by age, sex, ethnicity, and geographical location. Results provided evidence that all the genetic variants were significantly associated with breast cancer risk among North Indian women. Furthermore, on performing stratified analysis between breast cancer risk and different clinicopathological characteristics, we observed strong associations for menopausal status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, clinical stage, and histological grade. Our results suggest that these genes could be used as molecular markers to assess breast cancer susceptibility and predicting prognosis in North India population.

Evaluation of outcome and prognostic factors in extraosseous Ewing sarcoma

Data on extraosseous Ewing sarcoma (EES) with uniform chemotherapy protocol are minimal. We aimed to examine this aspect in our patients, identify prognostic factors and compare the same with osseous Ewing sarcoma.

Association of overweight and obesity with breast cancer in India

Background: In women, cancer of the breast is one of the most common incident cancer and cause of death from cancer. Anthropometric factors of weight, height, and body mass index (BMI) have been associated with breast cancer risk. Objectives: To study the association of overweight and obesity with breast cancer in India. Materials and Methods: A hospital-based matched case-control study was conducted. Three hundred and twenty newly diagnosed breast cancer patients and three hundred and twenty normal healthy individuals constituted the study population. The subjects in the control group were matched individually with the patients for their age ±2 years and socioeconomic status. Anthropometric measurements of weight and height were recorded utilizing the standard equipments and methodology. The paired ‘t’ test and univariate logistic regression analysis were carried out. Results: It was observed that the patients had a statistically higher mean weight, body mass index, and mid upper arm circumference as compared to the controls. It was observed that the risk of breast cancer increased with increasing levels of BMI. Overweight and obese women had Odds redio of 1.06 and 2.27, respectively, as compared to women with normal weight. Conclusions: The results of the present study revealed a strong association of overweight and obesity with breast cancer in the Indian population.