Dossier: Ovarian and prostate cancers
Serum tumor markers in the management of ovarian, endometrial and cervical cancer

https://doi.org/10.1016/j.biopha.2003.11.003Get rights and content

Abstract

CA 125 is the most reliable serum marker for ovarian carcinoma. Whereas its role in the screening of the malignancy is controversial, serum CA 125 assay is very useful for both the differential diagnosis of ovarian masses, particularly in postmenopause, and the monitoring of the response to chemotherapy and follow-up of patients with histologically proven ovarian carcinoma. Tumor-associated antigens other than CA 125, such as CA 19.9, CA 15.3 and TAG.72, firstly identified in gastro-intestinal or breast malignancies, have been detected also in tissue and serum samples from patients with ovarian carcinoma. In particular CA19.9 offers the advantage of high sensitivity for mucinous histotype, which often fails to express CA 125. Serum CA 125 correlates with the clinical course of disease better than the other antigens, and in patients with positive CA 125 assay at diagnosis the concomitant evaluation of CA 19.9 or CA 72.4 or CA 15.3 does not offer any additional benefit for monitoring ovarian carcinoma. Conversely, the serial measurements of these other antigens may represent an interesting biochemical tool for the management of patients with negative CA 125 assay. Serum αFP and βHCG are very useful in the preoperative evaluation and management of nondysgerminomatous ovarian germ cell tumors, whereas elevated serum inhibin levels can be detected in patients with granulosa cell tumors of the ovary. As for endometrial carcinoma, preoperative serum CA 125 levels correlate with stage, depth of myometrial invasion, histologic grade, cervical invasion, peritoneal cytology, lymph node status and clinical outcome. Moreover, serial CA 125 assay is a good indicator of disease activity and a useful biochemical tool for post-treatment surveillance of patients with endometrial carcinoma. SCC is the most reliable serum marker for squamous cell cervical carcinoma, and in patients with this malignancy pretreatment SCC levels are related to tumor stage, tumor size, depth of cervical invasion, lymph-vascular space involvement, lymph node status and clinical outcome. Serial SCC measurements parallel the response to radiotherapy and chemotherapy as well as the clinical course of disease after the completion of treatment. Serum CYFRA 21.1 seems to be less sensitive than serum SCC for squamous cell cervical carcinoma. Elevated CA 125 levels can be often detected in patients with cervical adenocarcinoma. The future for tumor marker research is represented by the emerging technologies of transcriptional profiling and proteomics.

Introduction

From a clinical point of view, the term of tumor marker is applied to all substances produced and released either by tumor cells or by host cells and whose presence may be detected in the serum or other biological fluids, behaving as an indicator of the presence of the tumor [1]. The ideal tumor marker should have a high sensitivity (SE) and a high specificity (SP), in order to discriminate cancer patients from healthy subjects or patients with benign conditions, and should be secreted into the circulation in concentrations proportional to tumor burden and activity. Even if very few currently used tumor markers can be considered ideal, some tumor-associated antigens mainly identified with the monoclonal antibody technology may represent useful biochemical tools for the management of patients with gynecological malignancies, and particularly of those with ovarian carcinoma.

The aim of this paper is to review literature data about the clinical relevance of tumor marker assay in the management of patients with ovarian, endometrial and cervical cancer (Table 1).

Section snippets

CA 125 and ovarian carcinoma diagnosis

CA 125 is an antigenic epitope on a high-molecular-weight glycoprotein expressed in coelomic epithelium during embryonic development and recognized by a monoclonal antibody developed against a human ovarian carcinoma cell line [2], [3]. In adult tissues, traces of CA 125 can be detected in fallopian tube, endometrium, and endocervix; moreover, reactive mesothelial cells of the adult peritoneum in areas of inflammation and adhesions have also been found to stain positive for this antigen at

CA 125

Elevation of serum CA 125 has been detected in a number of physiological and pathological conditions associated with endometrial proliferation, including menstrual cycle, pregnancy, endometriosis, and endometrial carcinoma [3]. In detail, raised CA 125 levels (>35 U/ml) have been reported in 11–33.9% of patients with this malignancy [104], [105], [106], [107], [108]. Ginath et al. [108] found that 21.4% of 28 patients with endometrioid endometrial carcinoma had elevated serum CA 125, whereas

SCC

SCC antigen, a subfraction of the glycoprotein TA-4 isolated from squamous cell cervical cancer tissues, is the most commonly used serum marker for cervical cancer [127], [132], [133], [134], [135], [136], [137], [138], [139], [140], [141]. Elevated antigen levels have been found in 27–87.7% of patients with SCC of the cervix, and the different positivity rates among the authors reflect the differences in the selected cut-off value for the antigen (ranging from 1.9 to 2.8 ng/ml) and in patient

Conclusions

In gynecological oncology ideal tumor markers, such as αFP and βHCG, have been detected only for the rare nondysgerminomatous ovarian germ cell tumors, whereas for the common ovarian, endometrial and cervical carcinoma, there are available some tumor-associated antigens, such as CA 125 and SCC, that can help the clinicians in the management of these tumors. The future for tumor marker research is represented by the emerging technologies of transcriptional profiling and proteomics [166], [167].

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