Aberrant Promoter Methylation of YAP Gene and its Subsequent Downregulation in Indian Breast Cancer Patients.

BACKGROUND: YAP, a potent oncogene and major downstream effector of the mammalian Hippo tumor suppressor pathway can act as either oncogene or tumor suppressor gene based on the type of tissue involved. Despite various studies, the role and mechanism through which YAP mediates its tumor suppressor or oncogenic effects are not yet fully understood. Therefore in the present study we aimed to investigate YAP at DNA, mRNA and protein level and also attempted to correlate our molecular findings with various clinicopathological variables of the patients. METHODS: The study comprised of a total 137 genetically unrelated women with sporadic breast cancer cases and normal adjacent tissues not infiltrated with tumor. Mutation of YAP gene was analyzed by automated DNA sequencing. YAP promoter methylation was studied using MS-PCR. Expression at mRNA and protein level was studied using qPCR and IHC respectively. RESULTS: In our study YAP mRNA expression was found to be 8.65 ± 6.17 fold downregulated in 67.15% cases. The expression of YAP when analyzed at the protein level by IHC was found to be absent in 78.83% cases. Results from MS-PCR analysis showed that YAP promoter methylation plays an important role in declining the expression of YAP protein. The absence of YAP protein coincided with 86.60% methylated cases thereby showing a very strong correlation (p = 0.001). We also investigated YAP mutation at the major check point sites in the Hippo pathway and observed no mutation. A significant association was observed on correlating mRNA expression with clinical stages (p = 0.038) and protein expression with ER status (p = 0.018) among Indian breast cancer patients. CONCLUSION: The expression of YAP was found to be downregulated in response to aberrant promoter methylation. The downregulation of YAP are consistent with previous studies suggesting it to have a tumor suppressive role in breast cancer. We did not observe any mutation at the major check point sites in the Hippo pathway.

Minimizing Post-operative Complications of Groin Dissection Using Modified Skin Bridge Technique: A Single-Centre Descriptive Study Showing Post-operative and Early Oncological Outcomes.

INTRODUCTION: Historically, groin dissections are associated with high morbidity. Various modifications have been described in the literature with inconsistent outcomes. The aim of this paper is to highlight modified skin bridge technique to minimize all post-operative complications of groin dissection without compromising early oncological outcomes. METHODS: A retrospective descriptive study of the computerized cancer database was performed to retrieve details of all the cancer patients who had undergone groin dissections during January 2012 to September 2016. Data pertaining to clinical profile including demographics, clinical and histopathological details, treatment profile, procedure-related morbidity and relapse patterns were extracted and analysed. RESULTS: A total of 75 patients underwent 105 groin dissections during this period. Out of 105 groin dissections, 43 were inguinal lymph node dissection (ILND) and 62 were combined ilio-inguinal lymph node dissection (IILND). The most common diagnosis was carcinoma penis (25%) followed by malignant melanoma (14.6%) and squamous cell carcinoma (13.33%) of lower extremities. Overall, the most common complications were seroma (14.28%) and skin edge necrosis (7.61%) followed by surgical site infection (4.76%). After a median follow-up of 17.64 months (IQR 5-61.53), a total of 18 patients (24%) developed recurrence. CONCLUSION: Groin dissection still remains an important diagnostic as well as therapeutic procedure justifying its potential of morbidity. Modified skin bridge technique is a very effective method to minimize all post-operative complications with optimal early oncological outcomes.

Staging PET-CT Scanning Provides Superior Detection of Lymph Nodes and Distant Metastases than Traditional Imaging in Locally Advanced Breast Cancer.

BACKGROUND: This study was designed to evaluate the role of a single 18-FDG positron emission tomography and computed tomography (PET-CT) scan in comparison to multiple organ-directed conventional investigations (CI) as a staging tool in locally advanced breast cancer (LABC) to detect regional and distant metastasis. METHODS: All eligible patients were subjected to CI (chest X-ray, abdominal sonography, and bone scintigraphy) followed by a single 18-FDG PET-CT scan. Standard imaging criteria were used for diagnosis of metastasis. Histopathological confirmation was undertaken for suspicious lesions. An exploratory analysis was done to assess the impact of PET-CT on the staging of LABC and how it resulted in a change in management. RESULT: The study included 79 patients of LABC. PET-CT detected distant metastasis in 36 (45.5 %) patients while CI could identify distant metastasis in 20 (25.3 %) patients. Two of the 36 patients in whom PET-CT detected distant metastasis were false positive. Overall PET-CT upstaged the disease in 38 (48.1 %) patients as compared to CI: stage III to stage IV migration in 14 (17.7 %) patients due to identification of additional sites of distant metastasis, and within stage III upstaging in 24 (30.3 %) patients due to identification of additional regional lymphadenopathy. PET-CT led to a change in management plan in 14 (17.7 %) patients. CONCLUSION: PET-CT has a role in identifying additional sites of regional lymphadenopathy and distant metastasis to upstage the disease in a significant number of LABC patients in comparison to CI; this would help in accurate staging, selecting optimal treatment, and better prognostication of disease.

Nuclear heterogeneous nuclear ribonucleoprotein D is associated with poor prognosis and interactome analysis reveals its novel binding partners in oral cancer.

BACKGROUND: Post-transcriptional regulation by heterogeneous ribonucleoproteins (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal mucosa; its role in oral carcinogenesis remains unknown. Here in we determined the hnRNPD associated protein networks and its clinical significance in oral squamous cell carcinoma (OSCC). METHODS: Immunoprecipitation (IP) followed by tandem mass spectrometry was used to identify the binding partners of hnRNPD in oral cancer cell lines. Ingenuity pathway analysis (IPA) was carried out to unravel the protein interaction networks associated with hnRNPD and key interactions were confirmed by co-IP-western blotting. hnRNPD expression was analyzed in 183 OSCCs, 44 oral dysplasia and 106 normal tissues using immunohistochemistry (IHC) and correlated with clinico-pathological parameters and follow up data over a period of 91 months. Kaplan-Meier survival and Cox-multivariate-regression analyses were used to evaluate the prognostic significance of hnRNPD in OSCC. RESULTS: We identified 345 binding partners of hnRNPD in oral cancer cells. IPA unraveled novel protein-protein interaction networks associated with hnRNPD and suggested its involvement in multiple cellular processes: DNA repair, replication, chromatin remodeling, cellular proliferation, RNA splicing and stability, thereby directing the fate of oral cancer cells. Protein-protein interactions of hnRNPD with 14-3-3ζ, hnRNPK and S100A9 were confirmed using co-IP-western blotting. IHC analysis showed significant overexpression of nuclear hnRNPD in oral dysplasia [p = 0.001, Odds ratio (OR) = 5.1, 95% CI = 2.1-11.1) and OSCCs (p = 0.001, OR = 8.1, 95% CI = 4.5-14.4) in comparison with normal mucosa. OSCC patients showing nuclear hnRNPD overexpression had significantly reduced recurrence free survival [p = 0.026, Hazard ratio = 1.95, 95% CI = 1.0-3.5] by Kaplan-Meier survival and Cox-multivariate-regression analyses and has potential to define a high-risk subgroup among OSCC patients with nodal negative disease. CONCLUSIONS: Our findings suggest novel functions of hnRNPD in cellular proliferation and survival, besides RNA splicing and stability in oral cancer. Association of nuclear hnRNPD with poor prognosis in OSCC patients taken together with its associated protein networks in oral cancer warrant future studies designed to explore its potential as a plausible novel target for molecular therapeutics.

Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients.

BACKGROUND: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and 5-year survival rates are about 50%. Identification of patients at high risk of recurrence will enable rigorous personalized post-treatment management. Most novel biomarkers have failed translation for clinical use because of their limited successful validation in external patient cohorts. The aim of this study was to determine the prognostic significance of alterations in sub-cellular expression of S100A2, a pro-tumorigenic calcium binding protein, identified as a candidate biomarker in our proteomic analysis in OSCC and validation of its clinical utility in an external cohort. METHODS: In a retrospective study, immunohistochemical analysis of S100A2 was carried out in 235 Indian OSCC (Test set) and 129 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 122 months for OSCC patients following the REMARK criteria. The findings were validated in an external cohort (Validation set 115 Canadian OSCC and 51 normal tissues) and data analyzed using the R package. RESULTS: Significant increase in cytoplasmic and decrease in nuclear S100A2 expression was observed in OSCC in comparison with normal tissues. Cox multivariable regression analysis internally and externally validated cytoplasmic S100A2 association with tumor recurrence. Kaplan Meier analysis of patients stratified to high and low risk groups showed significantly different recurrence free survival (Test set- log rank test, p = 0.005, median survival 16 and 69 months respectively and Validation set - p < 0.00001, median survival 9.4 and 59.9 months respectively); 86% and 81% of patients who had recurrence were correctly stratified into the high risk group. Seventy percent and 81% patients stratified into low risk group did not show cancer recurrence within 1 year in Test and Validation sets. CONCLUSIONS: Our study provided clinical evidence for the potential of cytoplasmic S100A2 overexpression as a predictor of recurrence risk in OSCC patients. A unique translational aspect of our study is validation of S100A2 as prognostic marker in two independent cohorts (Canadian and Indian) suggesting this protein is likely to find widespread utility in clinical practice for identifying oral cancer patients at high risk of disease recurrence.

Loss of DLC1 is an independent prognostic factor in patients with oral squamous cell carcinoma.

Deleted in liver cancer (DLC1), a Rho GTPase-activating protein, was observed to be differentially expressed in oral squamous cell carcinoma in comparison with normal tissues using tissue proteomics. In the current study, we investigated the clinical significance of loss of DLC1 expression in different stages of development of oral squamous cell carcinoma to determine its potential as a biomarker for oral dysplasia and prognosis of oral squamous cell carcinoma. Immunohistochemical analysis of DLC1 expression was carried out in oral squamous cell carcinoma patients (n=214), dysplasia (n=51), hyperplastic squamous mucosa (n=45), and histologically normal oral tissues (n=80), and correlated with clinicopathological parameters and disease prognosis over 91 months for oral squamous cell carcinomas. Loss of DLC1 expression was observed in oral squamous cell carcinoma (64%), oral dysplasia (31%), hyperplastic squamous mucosa (22%), and normal mucosa (16%). Significant loss of DLC1 expression was observed in oral squamous cell carcinomas as compared with dysplasia (P<0.001, odds ratio=3.8, 95% CI=2.0-7.3), suggesting it may be an important event involved in cancer progression. Among oral squamous cell carcinomas, the loss of DLC1 expression was significantly associated with poor prognosis (P=0.021, hazards ratio (HR)=1.8, 95% CI=1.1-2.9). Multivariate analysis revealed loss of DLC1 (P=0.023, HR=2.1, 95% CI=1.2-3.9) and histopathological grade (P=0.015, HR=1.7, 95% CI=1.1-2.7) to be independent predictors for disease-free survival in oral squamous cell carcinoma patients in comparison with known prognostic factors, viz. tumor stage, nodal status, and overall stage. Loss of DLC1 expression emerged as an important biomarker for predicting patients diagnosed with oral dysplasia at high risk of transformation upon future validation in longitudinal studies. Loss of DLC1 expression is a poor prognostic marker for oral squamous cell carcinoma patients.

Locally advanced sebaceous cell carcinoma (T3) of eyelid: incidence and pattern of nodal metastases and combined modality management approach.

BACKGROUND: Sebaceous carcinoma (SbCC) is a rare malignancy that often mimics benign conditions. Lymphatic involvement, large T3 tumors herald a dismal survival for patients. We present our series of 13 cases of locally advanced SbCC of the eyelid treated at a surgical oncology unit and describe the clinical profile, patterns of nodal spread and recurrence pattern in this subset of SbCC. METHODS: A retrospective analysis of case records was carried out for patients presenting with orbital tumors between January 1997 and April 2010 in the department of Surgical Oncology, AIIMS, New Delhi, India. All patients underwent orbital exenteration and superficial parotidectomy with neck dissection was added to patients with clinically significant lymphadenopathy. All patients who underwent OE after 2002 were advised radiotherapy as adjuvant therapy. The end point was development of recurrence or end of two year follow up period which ever occurred earlier. RESULTS: Thirteen patients underwent orbital exenteration. Eleven patients had clinically palpable lymphadenopathy. Ten patients (76.9%) had pathologically confirmed metastatic nodes. Parotid lymph node involvement was present in all patients (100%); two of these ten patients also had level II b cervical lymph node involvement. Recurrence was observed in seven patients (53.8%). All recurrences were loco-regional only and no systemic metastases was seen. There were only two recurrences in the group that received PORT. CONCLUSIONS: Eyelid SbCC is a loco-regionally aggressive malignancy and adequate disease control can be achieved with combined modality approach of radical surgery followed by post operative radiotherapy.

Basal cell adenocarcinoma of lacrimal gland.

Basal cell adenocarcinoma (BCAC) is a recently described rare salivary gland tumor. They are locally invasive and destructive tumors with rare incidence of metastasis. BCAC most commonly occur in the parotid gland followed by the submandibular and other minor salivary glands. The primary management of these tumors is surgery with or without adjuvant radiotherapy. Lacrimal gland is a very rare location of BCAC; only one case has been reported in English literature. We report a case of recurrent basal cell adenocarcinoma of lacrimal gland in a 75-year-old female. She had past history of local excision of a tumor in the lacrimal gland of same side 10 years back, details of which were not available with the patient. We discuss about the case and review the literature about treatment modality in basal cell adenocarcinoma.

Revisiting the role of computerized tomographic scan and cystoscopy for detecting bladder invasion in the revised FIGO staging system for carcinoma of the uterine cervix.

INTRODUCTION: Recent revision of the International Federation of Gynecology and Obstetrics (FIGO) staging system for the cervix encourages use of computerized tomography (CT) and magnetic resonance imaging and does not recommend cystoscopy as a mandatory investigation. But the revision has not defined which patients should undergo cystoscopy. Our study aims to revisit the role of CT scan and cystoscopy for detecting bladder invasion so that we can select patients for cystoscopy. METHODS: We reviewed case records of all cervical cancer patients who underwent abdominopelvic CT scan besides standard FIGO staging workup (including cystoscopy) and treatment with radiotherapy or concurrent chemoradiotherapy between years 2003 and 2005. Patients showing bladder invasion on CT scan or cystoscopy were identified and separately analyzed. Considering cystoscopy as the standard reference investigation, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CT scan for bladder invasion were calculated. RESULTS: A total of 305 case records were analyzed. Median age of the patients was 50 years (range, 25-85 years). Forty-three (14%) patients had bladder invasion on CT scan, and 17 (5.5%) had cystoscopy-confirmed invasion. No patient showing absence of bladder invasion on CT scan showed cystoscopy-confirmed invasion. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CT scan for bladder invasion were 100%, 92%, 40%, 100%, and 92%, respectively. The median overall survival of patients with CT-detected bladder invasion versus cystoscopy-confirmed invasion was 13 months versus 4 months, respectively (P = 0.007). CONCLUSIONS: Our results show that for cervical cancer, cystoscopy is not required in patients without any bladder invasion on CT scan. In the revised FIGO staging system, use of cystoscopy may be limited to patients having suspicious bladder invasion on CT scan. This will benefit both patient population and gynecologic oncologists, especially in developing countries with limited resources.

Genetic Polymorphism in TNF-α-308 G/A and TNF-ß +252 A/G, as Prognostic Biomarker in Breast Cancer Patients among Indian Population.

BACKGROUND: Cytokines are the key regulator molecules that modulate immune response. Tumor necrosis factor (TNF- α-308 G/A and TNF-ß +252 A/G ) are inflammatory cytokine that control the progression of several types of cancer. They play a vital role in both tumor progression and destruction based on their concentrations. The role of TNF-α-308 G/A and TNF-ß +252 A/G gene polymorphism in the etiology of breast cancer (BC) is not clearly understood. Therefore, present study investigates the association of TNF-α -308 G/A and TNF-ß +252 A/G and the clinical features with Breast cancer patients. METHODS: In a case- control study, we have investigated 150 breast cancer patients and 300 age and ethnically matched healthy controls for duration of 3 years from North India. Promoter polymorphisms of tumor necrosis factor gene (TNF-α -308 G/A and TNF-ß +252 A/G) were genotyped using allele specific oligonucleotide polymerase chain reaction ASO and restriction fragment length polymorphism (PCR-RFLP). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI) using SPSS. RESULTS: Patients with different clinico-pathological variables and healthy controls were analyzed. Significant association was observed in A allele of TNF-α -308 G/A in breast cancer patients as compared to healthy controls (p<0.0001). However, no association was seen in TNF-ß +252 A/G both at genotypic and allelic level. The GG genotype of TNF-ß +252A/G is higher in grades III (p<0.01) patients. CONCLUSION: Our results suggest that TNF-α-308G/A polymorphism showed significant association with breast cancer patients.

Clinical Spectrum, Pattern, and Level-Wise Nodal Involvement Among Oral Squamous Cell Carcinoma Patients - Audit of 945 Oral Cancer Patient Data.

Oral Squamous cell carcinoma (OSCC) is a locoregionally aggressive malignancy. Timely management of neck node dissemination, an important prognostic factor, impacts survival. The aim of the current study was to obtain comprehensive data on patterns or level-wise involvement of neck nodes to optimize neck management in OSCC. It was a retrospective analysis of a prospectively maintained database in a hospital-based setting. The current study evaluated patterns of spread to neck nodes in 945 pathologically proven OSCC patients who underwent neck dissection between 1995 and 2013. Clinical, surgical, pathological, level-wise information of neck nodes was available, and records of these patients were analyzed in relation to the pattern of involvement. Absolute/relative frequency distribution was used to describe the distribution of categorical variables. Continuous measures were organized as mean (standard deviation) and/or median (range). Buccal mucosa (28.78%) was the most common, whereas lip (5.08%) was the least common oral subsite. Modified neck dissection (69.75%) was the most common type of neck dissection. Pathological node positivity was documented in 39.8% patients and Level I(62.54%) and level II(57.33%) are the most common neck levels for nodal involvement. Involvement of Level III to V was seen less often (7.17%). There was no significant association between node positivity among different subsites of oral cancer. Neck level I and II are the most commonly involved levels. Sensitivity and specificity of clinical assessment are 83.51% and 30.05%, respectively. In view of this void in clinical assessment and a predictable nodal spread, alternate node assessment methodology must be explored.

Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma.

Oral leukoplakia is a heterogeneous lesion with risk of cancer development; there are no biomarkers to predict its potential of malignant transformation. Tissue proteomic analysis of oral leukoplakia using iTRAQ labeling liquid chromatography-mass spectrometry showed overexpression of heterogeneous ribonucleoprotein K (hnRNP K), a transformation-related RNA-binding protein, in leukoplakia in comparison with normal tissue. Herein, we investigated the clinical significance of hnRNP K in identification of oral leukoplakic lesions in early stages and as a prognostic marker in head-and-neck/oral squamous cell carcinomas (HNOSCCs). Immunohistochemical analysis of hnRNP K was performed in 100 HNOSCCs, 199 leukoplakias and 55 nonmalignant tissues and correlated with clinicopathologic parameters and disease prognosis over 6 years for HNOSCCs. hnRNP K nuclear expression increased from normal tissues to leukoplakia, and frank malignancy (p < 0.001). Cytoplasmic hnRNP K increased significantly from leukoplakia to HNOSCCs (p < 0.001) and was associated with poor prognosis of HNOSCCs (p = 0.011) by Kaplan-Meier analysis. The most important finding of our follow-up study is that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, whereas its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis, suggesting its putative utility in clinical management of HNOSCC.

Multimodality management of incidentally detected gall bladder cancer: long term results from a tertiary care cancer centre.

BACKGROUND: Gall bladder cancer (GBC) is the most common biliary tract malignancy in India. GBC present either with incidental diagnosis after simple cholecystectomy (SC) or with a primary gall bladder mass. Incidentally detected gall bladder cancer (ICGB) has traditionally been thought to be a relatively early stage disease but there are controversies associated with various aspects of its management. In this article we describe our experience with multimodality management of ICGB. METHODS: A retrospective analysis of incidentally detected GBC patients was performed to analyze the profile of presentation and treatment outcome. After initial radiological evaluation for operability, all the patients underwent surgical exploration. If found resectable, revision surgery including 2 cm wedge resection of liver and lymphadenectomy was done followed by concurrent chemo-radiation for tumors T2 and above stages. RESULTS: A total of 54 patients with incidentally detected GBC with a male to female ratio of 1:3 and mean age of 47.5 years were included in the study. Thirty-four (63%) patients underwent curative resection followed by adjuvant chemoradiotherapy. The remaining 20 patients had metastatic/unresectable disease. The 5 years disease free and overall survival (OS) for patients receiving curative treatment was 64% and 72% respectively. On univariate analysis, presence of residual disease in the gallbladder fossa and liver were significant risk factors for disease recurrence. Depth of invasion, adjuvant treatment received and stage were significant prognostic factors for OS. CONCLUSIONS: Incidentally detected GBC is increasing in incidence. A multi-modality approach with revision surgery and adjuvant chemo-radiation treatment may yield better outcome. Presence of residual disease is a poor prognostic factor. Optimal evaluation before SC and early referral to specialty center is therefore important in patients with suspicion of gallbladder malignancy because first chance is probably the best chance.

Hypermethylation analysis of mismatch repair genes (hmlh1 and hmsh2) in locally advanced breast cancers in Indian women.

Alterations in protooncogenes and tumor-suppressor genes at the DNA and/or protein level, which indicate the biological properties of individual breast cancers, led us to design a study encompassing the dilemma of "epigenetic silencing-driven genomic instabilities." In this study, we analyzed the promoter methylation of potent mismatch repair genes (hmlh1 and hmsh2) for the first time in 232 Indian patients with primary breast cancer (using methylation-specific polymerase chain reaction and expressional analysis). The study evaluates the gamut of epigenetic aberrations as well as genomic instabilities (microsatellite instabilities and loss of heterozygosity) and includes analysis of BAT-25, BAT-26, D2S123, D5S346, and D17S250. We observed hypermethylation of the hmlh1 gene in 43.5% of patients with primary breast cancer, of whom 66.9% had locally advanced breast cancer (stage IIIA, IIIB, and IIIC) (P < .0001). Similarly, we also found hypermethylation of the hmsh 2 gene in 16% of primary breast cancer cases. Of these patients, 21.3% had locally advanced breast cancer (P = . 01). To determine the effect of methylation, we also performed expressional studies using reverse transcriptase polymerase chain reaction and Northern blotting, but we were unable to get any significant expression in the presence of hypermethylation of either gene (hmlh1 and hmsh2). Interestingly, statistical analysis revealed that hypermethylation of the hmlh1 gene is one of the peculiar attributes of locally advanced breast cancer. In addition, this study indicates that for more sensitive stage-specific diagnosis or prognosis, both methylation of promoter and expression studies must be considered in the analyses in a reproducible manner. Therefore, pinpointing the methylation fingerprints (5'CpG island methylation) of potent DNA repairing genes not only shows the specific attributes of locally advanced breast cancer but also provides important insight into the mode of therapy to be used by clinical oncologists.

Operable Oral Tongue Squamous Cell Cancer: 15 Years Experience at a Tertiary Care Center in North India.

The aim of the present study was to provide insight into various demographic, clinical, and management profile of Indian patients with oral tongue squamous cell cancer (OTSCC). All the OTSCC patients who had undergone surgical treatment during 1995 to 2010 at a tertiary care center in North India were considered for the present study. The details of the patients were retrieved from a prospectively maintained computerized database. A total of 124 patients were included in the present study. Mean age of the patients was 50.4 ± 12.0 years. Lateral border of the tongue was the most common sub-site involved in 110 (88.7%) patients. Neck nodes were clinically palpable in 56.4% patients. Hemiglossectomy and anterior partial glossectomy were common surgical procedure undertaken in 57.2 and 25.8% patients. Negative resection margin was achieved in 97.5% patients. Pathological neck metastasis was seen in 40.3% patients. Occult neck metastasis was present in 25.9% patients among clinical N0 neck. At a mean follow-up of 29.8 months (SD 3.1), 20.1% developed disease relapse and 4.0% patients developed second primaries. Kaplan-Meier analysis estimated a 5-year disease-free survival of 81.5% and a 5 years overall survival of 78.6%. Cox proportional regression analysis predicted tumor size and number of positive nodes to be independent predictive variables for disease recurrence. Quality controlled surgery, coupled with adjuvant treatment when required, provides a safe and effective treatment of OTSCC with a good disease-free survival and loco-regional control.

Clinical Spectrum, Treatment and Relapse Patterns in 353 Patients with Squamous Cell Carcinoma of the Alveobuccal Complex Treated with a Curative Intent: A Retrospective Study.

AIMS AND OBJECTIVES: Oral cancer is one of the most common cancers in Indian subcontinent with alveobuccal complex as most common cancer sub site. Cancers of Alveobuccal complex provides maximum challenge and management guidelines are not clear. The aim of the present study is to provide comprehensive demographic, clinical and treatment outcome data of alveobuccal squamous cell carcinoma (SCC) patients treated at a tertiary care cancer center in North India. MATERIALS AND METHODS: An analysis of prospectively maintained database in department of surgical oncology at Dr BRA-IRCH, AIIMS, Delhi, India was performed. All alveobuccal cancer patients who had undergone surgery from 1995 to 2010 were included for analysis. RESULTS: A total of 353 patients were included for analysis. Mean age was 49.75 years (SD ±12.04) with male and female ratio of 4:1. Composite resection without mandible was done in 25 % patients and 75 % underwent mandibular resection. Neck dissection was performed in 347 patients. Nodal deposits were identified in 124 (35.73 %) neck dissection specimens. Margin negative resection was performed in 89.5 % cases. After a median follow up of 30 months, 87 (24.64 %) patients developed disease relapse and 25 (7.08 %) patients developed second primaries. Overall 5-year disease free survival (DFS) was 57.65 % and 5 year overall survival (OS) was 59.86 %. CONCLUSION: Among Indian oral cancer patients alveobuccal complex is most common sub site. Majority presents in locally advanced stage and reasonably good outcomes can be achieved with quality control surgery and judicious use of radiotherapy.

Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer and accounts for 10%-15% of all breast cancers in the west. There is a scarcity of data on ILC from the Indian subcontinent. This report intends to present the patterns of care, survival outcomes, and prognostic factors of ILC treated in a tertiary care institute. MATERIALS AND METHODS: This retrospective analysis included consecutive patients diagnosed with ILC and registered at our Institute between 2009 and 2016. RESULTS: We included 97 patients with a median age of 53 years (range 28-80). American Joint Committee on Cancer (7th edition) stage distribution was stage I-8.24%, stage II-45.36%, stage III- 34.10%, and stage IV-12.30%. Bilateral breast cancer was seen in 8 cases. Estrogen receptor, progesterone receptor, and HER 2/neu positivity was 90%, 85%, and 9%, respectively. Triple-negative breast cancer constituted 5% of cases. Twenty-nine events were recorded (systemic and locoregional relapse) with a median follow-up of 3.5 years. Three years relapse-free survival (RFS) and overall survival were 80% and 60%, respectively. Bones were the most common site of metastasis. Age <45 years [HR-1.4 (0.8-2.1), P < 0.001] and advanced clinical tumor stage [T4, HR-2.1 (1.1-3.8), P = 0.001] were associated with poor RFS. CONCLUSION: ILC constituted 2.5% of breast cancer cases at our institute. Triple negativity and HER-2/neu positivity were seen in 9% and 5% of cases, respectively. Age <45 years and advanced clinical tumor stage were associated with poor RFS.

Extraskeletal orbital mesenchymal chondrosarcoma: surgical approach and mini review.

Extraskeletal orbital mesenchymal chondrosarcoma (MC) is an extremely rare and highly aggressive tumour. It has characteristic radiological features and pathognomic histological biphasic pattern. Radical resection with negative margins is the mainstay of treatment; role of adjuvant chemotherapy and radiotherapy is yet not well defined. We report a rare case of 18-year-old man who was diagnosed to have orbital MC. He presented with locally advanced disease with no vision in the affected eye. He underwent right orbital exenteration; a transcranial intradural approach was used to divide the optic nerve, and the temporalis muscle flap was utilised to fill the exenterated orbit. Though optic nerve involvement is rare in orbital MCs, a transcranial approach may be used effectively to avoid traction on optic chiasma and ensure margin-free resection in case of optic nerve involvement up to orbital apex. Unfortunately, prognosis remains dismal in MCs despite treatment.

A Comparative Study of Clinical Profile and Relapse Patterns in TRIPLE-NEGATIVE and Non-Triple-Negative Breast Cancer Patients Treated with Curative Intent.

Molecular subtyping in breast cancer is recently emerging as an important determinant of treatment and outcomes, and triple negative breast cancer (TNBC) has been established as a distinct clinical entity with unique features and adverse outcomes. A retrospective analysis of a prospectively maintained computerized breast cancer database was performed, and all the non-metastatic female breast cancer patients undergoing potentially curative multimodality treatment between 2005 and 2012 were included for analysis. Patients with incomplete information regarding ER, PR, and HER2/neu status were excluded. All the eligible patients were divided into TNBC and non-TNBC group based on molecular subtyping. A comparative analysis between the two groups was performed to analyze the clinical spectrum and patterns of relapse. A total of 861 patients qualified for the final analysis and the proportion of TNBC was 254 (29.5%) and non-TNBC was 607 (70.5%). Patients in the TNBC group were slightly younger than the non-TNBC group (median age 46 vs. 49, p value = 0.006). TNBC group had a higher breast conservation surgery (BCS) rate, and there was no difference in the need for chemo and radiotherapy between two groups. The overall recurrence rates were significantly higher in TNBC group compared to non-TNBC group (26.8 vs. 19.3%, p value = 0.01). Local disease recurrences were significantly higher in TNBC compared to non-TNBC (7.9 vs. 3.1%, p value = 0.002). Both the regional and systemic recurrences were higher in TNBC group compared to non-TNBC, though the difference failed to attain statistical significance (for regional recurrences 2.4 vs. 1.5%, p value = 0.36; for systemic recurrences 23.2 vs. 17.8%, p value = 0.06). The brain metastasis was significantly higher in TNBC group (6.7 vs. 3.3%, p value = 0.02). In addition, time to relapse was also significantly less in TNBC cohort (16.1 vs. 22.1 months). TNBC accounts for almost one-third of the breast cancer patients with a relatively younger age at presentation, higher volume of disease burden and high breast conservation rates. Despite a standard multimodality therapy the local, systemic, and CNS recurrence rates are high in TNBC and majority relapse within first 2 years after completion of therapy.

Malignant peripheral nerve sheath tumors (MPNST)--clinicopathological study and treatment outcome of twenty-four cases.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is biologically an aggressive tumor for which the treatment of choice is the surgery. We reviewed the clinical profile, diagnostic methods, treatment patterns, and outcome of twenty-four MPNST patients in this study. PATIENTS AND METHODS: A retrospective analysis of 24 MPNST patients, treated from 1994 to 2002, in the department of Surgical Oncology at All India Institute of Medical Sciences, New Delhi, was done. A combination of gross, histopathological and immunohistochemical findings, and proliferation markers (MIB1) were considered for diagnosis and grade of the MPNST. Survival analysis was done by the Kaplan-Meier method and differences were evaluated with the log-rank test. Multivariate analysis was carried out by using Cox's proportional hazards model by using SPSS (Version 9, Chicago, Illinois) software. RESULTS: MPNST constituted 12% of all soft tissue sarcomas, where 21% (5/24) of patients had associated Von Recklinghausen's disease (VRHD). A higher incidence of male preponderance and multifocal MPNST were noted in the present series. At a mean follow-up of 38 months, 13 (54 %) patients had relapse of disease and 5-year over all and disease free survival were 58% and 35% respectively. In univariate analysis, sex (p = 0.05), tumor depth (p < 0.03), and cellular differentiation (p < 0.002) were shown to be adverse prognostic factors for disease free survival and sex (p = 0.04), cellular differentiation (p < 0.0004), and tumor grade (p = 0.05) for overall survival. However, in multivariate analysis, cellular differentiation (p < 0.005) and tumor grade (p < 0.01) emerged as independent prognostic factors for both disease free and overall survival, respectively. Postoperative radiotherapy (RT) has shown a definite role in both disease free and overall survival in this study. CONCLUSION: MPNSTs constituted a significant proportion (12%) of soft tissue sarcoma in our medical center. Heterogeneous differentiation and multifocality of the tumor were few distinct features of MPNST. Sex and cellular differentiation were noticed as the new adverse prognostic factors and adjuvant radiotherapy has been proved to be a significant treatment tool in the current series.