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Published on: August 2, 2024
Expression of beta-tubulin isotypes in human primary ovarian carcinoma
Yoshihiro Ohishi1, Yoshinao Oda, Yuji Basaki
1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Objective:
Selective expression of beta-tubulin isotypes has been reported to be one of the important mechanisms of taxane resistance. The purpose of this study was to evaluate the immunohistochemical expression of beta-tubulin isotypes using clinical samples of ovarian carcinoma treated by taxanes and to examine whether the protein levels of each of the beta-tubulin isotypes were correlated with the clinical features.
Experimental Design:
We examined tumor samples taken from 77 ovarian carcinoma patients (54 patients treated with a taxane-based regimen and 23 treated with a taxane-free regimen), for the intrinsic protein level of beta-tubulin isotype (classes I, II, III and IV) expression using immunohistochemistry, and we evaluated the correlation of this protein level with the clinical features. The expression levels were scored by the proportion and intensity of the immunoreactive tumor cells.
Results:
High protein levels of classes I and IV beta-tubulin, and very low protein levels of class II beta-tubulin, and intermediate protein levels of class III beta-tubulin expression were demonstrated in a total of 77 ovarian carcinomas. As for the samples taken from the 54 patients treated with the taxane-based regimen, 40 samples demonstrated undetectable levels of class II beta-tubulin protein. The class II beta-tubulin expression-absent group was significantly correlated with advanced stage (p=0.024) and with a short period of progression-free survival (log-rank test, p=0.022). Multivariate analyses demonstrated that the only significant independent prognostic indicator of a short period of progression-free survival was advanced stage, although a high expression of class III beta-tubulin was also prone to be associated with a short period of progression-free survival, but not significantly so (p=0.081). No such correlations or propensities were demonstrated in the 23 patients treated with the taxane-free regimen.
Conclusions:
In cases of ovarian carcinoma treated by taxanes, high expression of class III beta-tubulin seems to be associated with earlier recurrence, which is believed likely to be resistant relapse. In addition, loss of class II beta-tubulin expression is correlated with advanced stage, which may represent aggressive tumor progression.
Insights
In ovarian cancer treated with taxanes, high class III beta-tubulin expression correlates with earlier recurrence, suggesting taxane resistance. Loss of class II beta-tubulin is linked to advanced stage and aggressive tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Selective expression of beta-tubulin isotypes is a known mechanism of taxane resistance in cancer.
- Understanding these isotype expressions is crucial for predicting treatment response in ovarian carcinoma.
Purpose of the Study:
- To evaluate immunohistochemical expression of beta-tubulin isotypes in ovarian carcinoma patient samples treated with taxanes.
- To correlate beta-tubulin isotype protein levels with clinical features and treatment outcomes.
Main Methods:
- Immunohistochemistry was used to analyze beta-tubulin isotype (classes I, II, III, IV) protein levels in 77 ovarian carcinoma tumor samples.
- Samples were from patients treated with either taxane-based (n=54) or taxane-free (n=23) regimens.
- Expression levels were scored based on the proportion and intensity of immunoreactive tumor cells.
Main Results:
- High expression of beta-tubulin classes I and IV, low class II, and intermediate class III were observed across all samples.
- Undetectable class II beta-tubulin was found in 40/54 patients treated with taxanes and correlated significantly with advanced stage and shorter progression-free survival.
- High class III beta-tubulin expression showed a trend towards shorter progression-free survival, though not statistically significant.
Conclusions:
- High class III beta-tubulin expression in taxane-treated ovarian cancer may indicate earlier recurrence and potential taxane resistance.
- Loss of class II beta-tubulin expression is associated with advanced stage, suggesting a link to aggressive tumor progression.
