S Umesh

Publications of S Umesh

• Shift in AP-2alpha localization characterizes astrocytoma progression.

  Authors: Ramona Britto, S Umesh, A S Hegde, Sridevi Hegde, Vani Santosh, B A Chandramouli, Kumaravel Somasundaram

  Cancer biology & therapy. 04/2007; 6(3):413-8.

  Activator protein 2alpha (AP-2alpha) has been shown to be lost in the advanced stages of many cancers, including gliomas. In this study, we wanted to analyze the expression of AP-2alpha inActivator protein 2alpha (AP-2alpha) has been shown to be lost in the advanced stages of many cancers, including gliomas. In this study, we wanted to analyze the expression of AP-2alpha in astrocytoma samples of different grades both at the RNA level, by real-time qPCR and at the protein level, by immunohistochemistry, and to examine its correlation, if any, with patient outcome. Five Grade I, 14 Grade II, 18 Grade III, 72 Grade IV samples and 13 normal brain controls were included. We did not find any clear pattern of regulation at the RNA level with tumor grade. The RNA expression levels however, correlated to a large extent with the nuclear AP-2alpha staining in these samples (72.09%; 31/43). Further, we did not find a complete loss of nuclear AP-2alpha expression in the higher grades, in contrast to previous reports. Interestingly, we found cytoplasmic AP-2alpha expression in a majority of higher grade astrocytomas (Grade IV-85%; 33/39 and Grade III-74%; 14/19) in comparison to lower grades (Grade I-0%; 0/5 and Grade II-37.5%; 3/8) suggesting that the translocation of this protein from the nucleus to the cytoplasm may be responsible for the increased malignancy. The nuclear expression in these grades was found to be concomitantly reduced. Within GBMs, we found that decreased nuclear expression was indicative of a better prognosis. The striking observation was the shift in localization of this protein from the nucleus to the cytoplasm with increasing tumor grade, pointing to a crucial role for this transcription factor in the progression of astrocytomas.

• Shift in $AP-2\alpha$ Localization Characterizes Astrocytoma Progression

  Authors: Ramona Britto, S Umesh, AS Hegde, Sridevi Hegde, Vani Santosh, BA Chandramouli, Kumaravel Somasundaram

  Activator protein $2\alpha$ $(AP‑2\alpha)$ has been shown to be lost in the advanced stages of many cancers, including gliomas. In this study, we wanted to analyze the expression of $(AP‑2\alpha)$ inActivator protein $2\alpha$ $(AP‑2\alpha)$ has been shown to be lost in the advanced stages of many cancers, including gliomas. In this study, we wanted to analyze the expression of $(AP‑2\alpha)$ in astrocytoma samples of different grades both at the RNA level, by real‑time qPCR and at the protein level, by immunohistochemistry, and to examine its correlation, if any, with patient outcome. Five Grade I, 14 Grade II, 18 Grade III, 72 Grade IV samples and 13 normal brain controls were included. We did not find any clear pattern of regulation at the RNA level with tumor grade. The RNA expression levels however, correlated to a large extent with the nuclear $(AP‑2\alpha)$ staining in these samples (72.09%; 31/43). Further, we did not find a complete loss of nuclear $(AP‑2\alpha)$ expression in the higher grades, in contrast to previous reports. Interestingly, we found cytoplasmic $(AP‑2\alpha)$ expression in a majority of higher grade astrocytomas (Grade IV—85%; 33/39 and Grade III—74%; 14/19) in comparison to lower grades (Grade I—0%; 0/5 and Grade II—37.5%; 3/8) suggesting that the translocation of this protein from the nucleus to the cytoplasm may be responsible for the increased malignancy. The nuclear expression in these grades was found to be concomitantly reduced. Within GBMs, we found that decreased nuclear expression was indicative of a better prognosis. The striking observation was the shift in localization of this protein from the nucleus to the cytoplasm with increasing tumor grade, pointing to a crucial role for this transcription factor in the progression of astrocytomas.

• Clinical and immunohistochemical prognostic factors in adult glioblastoma patients.

  Authors: S Umesh, A Tandon, V Santosh, B Anandh, S Sampath, B A Chandramouli, V R Sastry Kolluri

  Clinical neuropathology. 28(5):362-72.

  OBJECTIVE: Glioblastomas are the commonest and the most malignant of all adult brain tumors, characterized by genetic instability, intratumoral histopathological variability, and unpredictableOBJECTIVE: Glioblastomas are the commonest and the most malignant of all adult brain tumors, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. The utility of tumor markers that reflect their underlying biology is becoming increasingly important with respect to patient prognostication and their potential role as molecular targets of therapy is being recognized. In this study, we aimed to identify the clinical factors and some immunohistochemical markers that could have an effect on patient survival in supratentorial glioblastomas. MATERIALS AND METHODS: We evaluated 54 cases of adult supratentorial glioblastomas operated over a span of 1 year, with respect to clinical features such as age, Karnofsky performance score (KPS), extent of resection, adjuvant therapy, and immunohistochemical expression of p53, EGFR (Epidermal Growth Factor Receptor) and PTEN (Phosphatase and Tensin homolog). RESULTS: Radiotherapy and KPS at presentation were significant predictors of outcome in both univariate and multivariate analyses. Among immunohistochemical variables; loss of PTEN expression in association with over-expression of EGFR showed a trend towards poorer survival, in univariate analysis. Over-expression of EGFR and/or p53 emerged as significant predictors of poor outcome on multivariate analysis, despite failing to prognosticate on univariate analysis. CONCLUSIONS: Our study shows that EGFR and p53 overexpression along with loss of PTEN expression are important adjuncts to clinical variables in prognosticating glioblastoma patients.