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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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WWOX immunohistochemical staining of normal ovary. A) Representative photomicrograph (20X) of normal ovary displaying positive staining in ovarian surface epithelial cells. B) Photomicrograph (20X) showing strong WWOX inmunostaining localizing to the cytoplasm of inclusion cyst epithelial cells.
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Figure 2: WWOX immunohistochemical staining of normal ovary. A) Representative photomicrograph (20X) of normal ovary displaying positive staining in ovarian surface epithelial cells. B) Photomicrograph (20X) showing strong WWOX inmunostaining localizing to the cytoplasm of inclusion cyst epithelial cells.

Mentions: The analysis of TMA cores and whole sections of normal human ovary showed that WWOX protein is constitutively expressed at high levels in normal OSE cells (Figure 2A), in epithelial inclusion cysts within the cortex (Figure 2B) and in scattered granulosa-lutein cells surrounding aged corpora lutea or corpora albicans (not shown). Positive staining was also detected in one observed Walthard nest within the ovarian hilus and in a few stromal cell patches likely related with hormone production. In all cases the inmunostaining had a homogeneous and diffuse pattern that was localized to the cytoplasm.


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)

WWOX immunohistochemical staining of normal ovary. A) Representative photomicrograph (20X) of normal ovary displaying positive staining in ovarian surface epithelial cells. B) Photomicrograph (20X) showing strong WWOX inmunostaining localizing to the cytoplasm of inclusion cyst epithelial cells.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: WWOX immunohistochemical staining of normal ovary. A) Representative photomicrograph (20X) of normal ovary displaying positive staining in ovarian surface epithelial cells. B) Photomicrograph (20X) showing strong WWOX inmunostaining localizing to the cytoplasm of inclusion cyst epithelial cells.
Mentions: The analysis of TMA cores and whole sections of normal human ovary showed that WWOX protein is constitutively expressed at high levels in normal OSE cells (Figure 2A), in epithelial inclusion cysts within the cortex (Figure 2B) and in scattered granulosa-lutein cells surrounding aged corpora lutea or corpora albicans (not shown). Positive staining was also detected in one observed Walthard nest within the ovarian hilus and in a few stromal cell patches likely related with hormone production. In all cases the inmunostaining had a homogeneous and diffuse pattern that was localized to the cytoplasm.

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