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WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome.

Nunez MI, Rosen DG, Ludes-Meyers JH, Abba MC, Kil H, Page R, Klein-Szanto AJ, Godwin AK, Liu J, Mills GB, Aldaz CM - BMC Cancer (2005)

Bottom Line: Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels.The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types.It was also observed that subsets of ovarian tumors demonstrated loss of WWOX expression and is potentially associated with patient outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Carcinogenesis, The University of Texas M,D, Anderson Cancer Center, Science Park-Research Division, Smithville TX, USA. minunez@mdanderson.org <minunez@mdanderson.org>

ABSTRACT

Background: The putative tumor suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D) at chromosome area 16q23.3-24.1. This region is a frequent target for loss of heterozygosity and chromosomal rearrangement in ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias. The goal of these studies was to evaluate WWOX protein expression levels in ovarian carcinomas to determine if they correlated with clinico-pathological parameters, thus providing additional support for WWOX functioning as a tumor suppressor.

Methods: We performed WWOX protein expression analyses by means of immunobloting and immunohistochemistry on normal ovaries and specific human ovarian carcinoma Tissue Microarrays (n = 444). Univariate analysis of clinical-pathological parameters based on WWOX staining was determined by chi2 test with Yates' correction. The basic significance level was fixed at p < 0.05.

Results: Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels. The immunohistochemistry of normal human ovarian tissue sections confirmed strong WWOX expression in ovarian surface epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444 ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely detectable WWOX expression. The remaining ovarian carcinomas (70%) stained moderately to strongly positive for this protein. The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types. Reduced WWOX expression demonstrated a significant association with clinical Stage IV (FIGO) (p = 0.007), negative Progesterone Receptor (PR) status (p = 0.008) and shorter overall survival (p = 0.03).

Conclusion: These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets of ovarian tumors demonstrated loss of WWOX expression and is potentially associated with patient outcome.

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Kaplan Meier Plot analysis showing the pattern of Overall Survival relative to WWOX protein expression.
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Figure 4: Kaplan Meier Plot analysis showing the pattern of Overall Survival relative to WWOX protein expression.

Mentions: An analysis of WWOX protein expression relative to disease relapse was performed in a subset of cases from the MDACC TMA (n = 354). Between relapsing and non-relapsing cases no statistical difference was observed regarding WWOX expression (p = 0.094) (Table 2). Among cases with progressive disease, 46% (27/59) showed negative/low WWOX levels of expression while 54% (32/59) fell in the positive category. It was possible to evaluate survival in cases from the MDACC group as shown by the Kaplan-Meier plot (Figure 4). Importantly, we observed a statistically significant correlation of WWOX expressing cases with longer overall survival and loss of WWOX protein expression correlated with shorter overall survival (p = 0.03).


WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome.

Nunez MI, Rosen DG, Ludes-Meyers JH, Abba MC, Kil H, Page R, Klein-Szanto AJ, Godwin AK, Liu J, Mills GB, Aldaz CM - BMC Cancer (2005)

Kaplan Meier Plot analysis showing the pattern of Overall Survival relative to WWOX protein expression.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1173095&req=5

Figure 4: Kaplan Meier Plot analysis showing the pattern of Overall Survival relative to WWOX protein expression.
Mentions: An analysis of WWOX protein expression relative to disease relapse was performed in a subset of cases from the MDACC TMA (n = 354). Between relapsing and non-relapsing cases no statistical difference was observed regarding WWOX expression (p = 0.094) (Table 2). Among cases with progressive disease, 46% (27/59) showed negative/low WWOX levels of expression while 54% (32/59) fell in the positive category. It was possible to evaluate survival in cases from the MDACC group as shown by the Kaplan-Meier plot (Figure 4). Importantly, we observed a statistically significant correlation of WWOX expressing cases with longer overall survival and loss of WWOX protein expression correlated with shorter overall survival (p = 0.03).

Bottom Line: Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels.The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types.It was also observed that subsets of ovarian tumors demonstrated loss of WWOX expression and is potentially associated with patient outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Carcinogenesis, The University of Texas M,D, Anderson Cancer Center, Science Park-Research Division, Smithville TX, USA. minunez@mdanderson.org <minunez@mdanderson.org>

ABSTRACT

Background: The putative tumor suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D) at chromosome area 16q23.3-24.1. This region is a frequent target for loss of heterozygosity and chromosomal rearrangement in ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias. The goal of these studies was to evaluate WWOX protein expression levels in ovarian carcinomas to determine if they correlated with clinico-pathological parameters, thus providing additional support for WWOX functioning as a tumor suppressor.

Methods: We performed WWOX protein expression analyses by means of immunobloting and immunohistochemistry on normal ovaries and specific human ovarian carcinoma Tissue Microarrays (n = 444). Univariate analysis of clinical-pathological parameters based on WWOX staining was determined by chi2 test with Yates' correction. The basic significance level was fixed at p < 0.05.

Results: Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels. The immunohistochemistry of normal human ovarian tissue sections confirmed strong WWOX expression in ovarian surface epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444 ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely detectable WWOX expression. The remaining ovarian carcinomas (70%) stained moderately to strongly positive for this protein. The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types. Reduced WWOX expression demonstrated a significant association with clinical Stage IV (FIGO) (p = 0.007), negative Progesterone Receptor (PR) status (p = 0.008) and shorter overall survival (p = 0.03).

Conclusion: These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets of ovarian tumors demonstrated loss of WWOX expression and is potentially associated with patient outcome.

Show MeSH
Related in: MedlinePlus