Sarcomatoid carcinomas are biphasic tumors proven to be monoclonal dedifferentiated forms of conventional squamous carcinomas. This study evaluates their clinicopathologic characteristics in head and neck mucosal sites and the problems in distinguishing them from other spindle cell tumors. A total of 103 cases with a confirmed diagnosis of sarcomatoid carcinoma accessioned in the pathology department of a tertiary referral cancer centre over a period of 7 years (2004)(2005)(2006)(2007)(2008)(2009)(2010) were studied. An algorithm used for their diagnosis is presented. Ages of the patients were 22-90 years (median 53 years), and male:female ratio was 3.7:1. Site distribution was oral cavity (n = 65, 63.1%), larynx (18, 17.5%), oropharynx/hypopharynx (12, 10.7%), maxilla (6, 5.8%) and metastatic nodes (2, 1.9%). A large number of patients (95%) presented with a mass lesion of less than 1 year duration. Histopathologically, epithelial differentiation was evident on morphology in 48 (46.6%) cases, only on IHC in 34 (33%) cases, and in 21 (20.4%) no epithelial differentiation was seen. Typically, tumors were polypoidal (92, 89.3%) and ulcerated (95, 92.2%) with cells arranged predominantly in fascicles (59, 57.3%) or storiform pattern (17, 16.5%) amidst collagenous (50, 48.5%) or myxoid matrix (35, 34%). Anaplasia (2?/3?) and mitosis[10 per 10 HPF were noted in 96 (93.2%) cases. IHC was done in 82 cases; 55 (66.7%) showed positivity for epithelial markers with aberrant expression of mesenchymal markers in 43 (41.7%). Diagnosis of sarcomatoid squamous carcinoma is challenging because of overlapping histopathological features with other spindle cell tumors. Understanding their clinicopathologic characteristics facilitates their diagnosis and appropriate clinical management.

We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1 (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis.

The molecular mechanisms contributing to the development and progression of gingivobuccal complex (GBC) cancers–a sub-site of oral cancer, comprising the buccal mucosa, the gingivobuccal sulcus, the lower gingival region and the retromolar trigone-remain poorly understood. Identifying the GBC cancer-related gene expression signature and the driver genes residing on the altered chromosomal regions is critical for understanding the molecular basis of its pathogenesis. Genome-wide expression profiling of 27 GBC cancers with known chromosomal alterations was performed to reveal differentially expressed genes. Putative driver genes were identified by integrating copy number and gene expression data. A total of 315 genes were found differentially expressed (P≤0.05, logFC>2.0) of which eleven genes were validated by real-time quantitative reverse transcriptase-PCR (qRT-PCR) in tumors (n=57) and normal GBC tissues (n=18). Overexpression of LY6K, in chromosome band 8q24.3, was validated by immunohistochemical (IHC) analysis. We found that 78.5% (2,417/3,079) of the genes located in regions of recurrent chromosomal alterations show copy number dependent expression indicating that copy number alteration has a direct effect on global gene expression. The integrative analysis revealed BIRC3 in 11q22.2 as a candidate driver gene associated with poor clinical outcome. Our study identified previously unreported differentially expressed genes in a homogeneous subtype of oral cancer and the candidate driver genes that may contribute to the development and progression of the disease.

BackgroundHuman sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyzed subtype-specific variation of hNIS overexpression in breast tumor tissue samples by immunohistochemistry (IHC) and also report the development of a homogeneous, quantitative analysis method of digital IHC images.MethodshNIS expression was analyzed from 108 BC tissue samples by IHC. Sub-cellular localization of hNIS protein was analyzed by dual immunofluorescence (IF) staining method using hNIS and HER2 antibodies. An ImageJ based two-step digital analysis method was developed and applied for the bias-free analysis of the images.ResultsStaining of the tumor samples show 70% cases are hNIS positive indicating high incidence of hNIS positive cases in BC. More importantly, a subtype specific analysis done for the first time shows that hNIS expression is overly dominated in estrogen receptor (ER) positive cases than the receptor negative cases. Further, 56% of the ER+ve, PgR+ve, HER2-ve and 36% of ER+ve, PgR+ve, HER2+ve cases show highest intensity staining equivalent to the thyroid tissue. A significant positive correlation is also observed between hNIS and estrogen receptor expression (p = 0.0033, CI = 95%) suggesting hNIS mediated targeted radio-iodine therapy procedures may benefit both ER+ve, PgR+ve, HER2–ve as well as HER2+ve cases. Further, in a few cases, hNIS and HER2 protein localization is demonstrated by overlapping membrane co-expression. ImageJ based image analysis method shows over 70% match with manual pathological scoring method.ConclusionThe study indicates a positive link between hNIS and ER expression in BC. The quantitative IHC image analysis method reported here will further help in patient stratification and potentially benefit global clinical assessment where hNIS mediated targeted 131I radio-ablative therapy is aimed.

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