Increased nuclear accumulation of pSTAT3 occurs in early premalignant stages and is a marker for poor prognosis of OSCC.

Context.-Ocular surface squamous neoplasia (OSSN) is the most common tumor of conjunctival epithelium associated with risk of permanent visual impairment. It includes conjunctival intraepithelial neoplasia and squamous cell carcinoma. Although American Joint Committee on Cancer-TNM (AJCC-TNM) staging is commonly used in various tumors, it has only recently been described for OSSN.Objectives.-To evaluate the prognostic relevance of AJCC-TNM staging and the clinicopathological features in OSSN.Design.-Sixty-four histopathologically proven cases of OSSN (20 conjunctival intraepithelial neoplasia and 44 squamous cell carcinoma) were included in the study. The AJCC-TNM staging and clinicopathological features of OSSN cases were recorded. Patients were followed up for 17 to 40 months (median, 32 months). Univariate and multivariate analyses were performed to determine the prognostic value of various clinicopathological features.Results.-Longer sunlight exposure (P ¼ .01), diffuse growth pattern (P ¼ .02), larger tumor size (2 cm) (P ¼ .03), histopathological diagnosis of squamous cell carcinoma (P ¼ .02), and orbital invasion or invasion of adjacent structures (T3 or T4) (P , .001) emerged as significant predictors of reduced recurrence-free survival. Using multivariate analysis, a higher T category (T3 or T4) was the most important prognostic indicator of a poor outcome.Conclusions.-A higher T category (T3 or T4) is an important predictor of clinical outcome, and the use of the AJCC-TNM staging system is recommended in the management of all patients with OSSN. Longer sunlight exposure, larger tumor size (2 cm), orbital invasion or invasion of adjacent structures (T3 or T4), and a histopathological diagnosis of squamous cell carcinoma are other clinicopathological features of prognostic relevance in patients with OSSN.

Background Although human papillomavirus (HPV) has been implicated in the pathogenesis of ocular surface squamous neoplasia (OSSN), no study has so far dealt with the prognostic role of HPV. In this study the presence and significance of HPV in OSSN and its correlation with p16INK4a immunoexpression was determined. Methods HPV was detected by HPV-L1 capsid genespecific multiplex PCR using PGMY09/11 primers, and genotyping was done by linear array on 64 OSSN patients and 15 conjunctival controls. p16INK4a immunoexpression as a marker for HPV presence was also evaluated. Results The HPV genome was detected in 11% of cases by multiplex PCR, and all positives belonged to a high-risk HPV16 genotype. p16INK4a Overexpression was seen in 28% (18/64) of cases. Control conjunctival tissues were negative for HPV and p16INK4a expression. The presence of HPV was associated with significantly improved disease-free survival ( p=0.02) as well as p16INK4a overexpression ( p=0.001). The sensitivity and specificity of p16INK4a as a marker for HPV presence was 86% and 79%, respectively, with a positive predictive value of 33% and a negative predictive value of 98%. Conclusions The results of this study point towards HPV as a predictor of better survival in a subset of HPV-positive OSSN patients. Although p16 INK4a immunoexpression is a useful indicator of HPV presence in OSSN, confirmation by multiplex PCR is necessary.

Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation. Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose. Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.