We read with great interest the Martín de la Fuente et al (1) article on assessing the prognostic significance of claudin-4 overexpression in patients with ovarian carcinoma. The authors concluded that claudin-4 was a potential prognostic biomarker in ovarian carcinoma, but, according to their findings, it did not seem to play a significant role in predicting platinum-based treatment protocol resistance.
Considering the role of claudin-4 prognostically, this clearly presents an inconsistency worth further discussion. We believe it could partly be explained by the fact that the study cohort is not a uniform group but rather a mixed group of high-grade serous carcinomas and non-high-grade serous carcinomas (i.e. low-grade serous, endometriod, clear cell, mucinous, etc.).
This may present a source of bias in the analysis, as it is known that some ovarian tumors (most notably serous border-line tumors) are platinum resistant, as originally shown by the Norwegian Radium Hospital study in 1993 (2). In the Martín de la Fuente and colleagues study, 70% of the patients (n= 80) had high-grade serous carcinoma, with 55% showing claudin-4 overexpression (vs. 45% with claudin-4 low-expression).
We suppose a further comparative analysis of these high-grade serous carcinoma patients would provide more information concerning the claudin-4 prognostic value and treatment response predictive value in ovarian carcinomas. We believe that the Martín de la Fuente and colleagues article is an outstanding study that may also provide important information on the question raised by Dao et al (3) on the as yet unexplained long-term survival (>10 years) of some of the patients with high-grade serous carcinoma.
Although a sample of 80 patients with high-grade serous carcinoma may be rather small, we suppose Martín de la Fuente and colleagues are still in a good position to provide their point of view on highly demanded information regarding survival prognosis in patients with high-grade serous ovarian carcinomas and its possible correlation with claudin-4 expression.