CYFRA 21-1 is a soluble serum fragment of cytokeratin 19. In a retrospective study, CYFRA 21-1 was measured along with the tumour markers CA72-4, CASA and the established marker CA125 II in stored serum obtained from 72 women with ovarian cancer at primary diagnosis. Measurement of CYFRA 21-1 had a sensitivity of 44% which was similar to that obtained by the other markers: CA125 II 47%; CA72-4 47%; CASA 31%. The sensitivity of CYFRA 21-1 was 33% in serous ovarian cancer and 36% in mucinous ovarian cancer (Hasholzner et al 1994, 1996). A study in Japan measured CYFRA 21-1 together with CA125 and squamous carcinoma antigen initially in 102 healthy Japanese women to set the reference value and then in 94 women with benign gynaecological disease and 141 women with malignant disease (Inaba et al 1995). The respective positivity rates for CYFRA 21-1 and CA125 were 64% and 77% in ovarian malignancy, while they were 4 and 31% in benign ovarian masses. As a marker, CYFRA 21-1 had an accuracy of 61% in diagnosing ovarian malignancy, which was higher than that of CA125 (53%). The positive predictive value (PPV) of CYFRA 21-1 for ovarian cancer of 94% was significantly higher than the PPV of 69% achieved with CA125. The potential usefulness of CYFRA 21-1 as a tumour marker for ovarian malignancy needs to be explored further before any firm conclusions can be drawn.
In ovarian cancer patients elevated levels of a 6 kDa polypeptide, the tumour-associated trypsin inhibitor (TATI), have been detected in both urine and serum. When used as a single marker in 180 patients with epithelial ovarian cancer and 214 women with benign pelvic pathology, serum TATI achieved a lower sensitivity (63%) and specificity (72%) than CA125 (>35 U/ml). A combination of the two markers increased the sensitivity to 91% but the specificity decreased to 65%. However, the use of TATI was clearly superior in diagnosing mucinous adenocarcinoma of the ovaries, the rate of true positive findings being 64% compared with 50% for CA125. Unlike CA125, TATI levels correlated well with tumour grade. While CA125 remains the single tumour marker of choice in the diagnosis of malignant epithelial ovarian cancer, TATI appears to be a possible complementary marker with a higher sensitivity in cases of poorly differentiated and mucinous carcinoma (Peters-Engl et al 1995). It may also have a role to play in predicting prognosis. When assayed prior to surgery in 66 patients with stage III and IV ovarian cancer, serum TATI levels were elevated in 41%. These women had a 5-year cumulative survival rate of 8%, whereas the survival rate was 45% in the 39 patients with normal preoperative TATI values. In contrast, the preoperative CA125 levels in these women did not predict survival. In multivariate analysis which included age, stage, histological grade and preoperative TATI and CA125 levels, patients with elevated preoperative TATI levels had a 2.3-fold relative risk of death compared with patients with normal preoperative levels. Thus, preoperative determination of serum TATI may have a place in the pretreatment evaluation of patients with advanced ovarian cancer (Venesmaa et al 1994).
Multiple serum markers have been assessed in isolation and in various combinations in women with ovarian cancer, both in the context of screening and in assessing prognosis and monitoring response and recurrence. The most significant finding is that in women with ovarian cancer, no single agent or combination has emerged as having a clear clinical advantage over CA125, except in specific tumour subtypes such as germ-cell tumours with yolk sac or chorionic elements and granulosa cell tumours (Table 2).
There are no serum tumour markers with a well-established role in clinical management of endometrial cancer. Serum CA125 levels are elevated in 10-27% of patients with endometrial carcinoma (Patsner et al 1990, Takeshima et al 1994, Hakala et al 1995). In two series of 42 and 148 women, respectively, with endometrial cancer (Gadducci et al 1990, Tomas et al 1990), the incidence of elevated serum CA125 levels was significantly greater in advanced-stage disease (63-67%) than in early-stage disease (10-19%). Thus CA125 measurement prior to surgery may be useful in predicting the presence of extrauterine and metastatic spread. Serum CA125 levels may have a role in surveillance following treatment of patients with early-stage endometrial carcinoma, but may be falsely elevated in the presence of severe radiation injury. Isolated recurrences in the vagina do not cause elevation, while distant metastasis normally does.
Among the general tumour markers for gynaecological malignancy, CYFRA 21-1 was found to be elevated in 52% of endometrial malignancies (Inaba et al 1995) and urinary p-core or UGF levels were elevated in 38-48% of samples from women with endometrial carcinoma (Kinugasa et al 1995, Cole et al 1996).
Screening for cervical cancer uses exfoliative cytology and currently there are no serological markers being explored in this context. However, in assessing
Table 2 Role of current tumour markers in ovarian cancer
Ovarian cancers Screening Differential Prognostic Monitoring Detection of diagnosis indicator response to recurrence treatment
Epithelial CA125 as part of
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