M. Krans

Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas.

PURPOSE To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.

Higher levels of interleukin‐6 in cystic fluids from patients with malignant versus benign ovarian tumors correlate with decreased hemoglobin levels and increased platelet counts

Background. Recently, high pretreatment platelet counts and low pretreatment hemoglobin levels were found to be negative prognostic factors in patients with ovarian cancer. Interleukin‐6 (IL‐6) is a multifunctional cytokine with a diversity of functions leading to the induction of C‐reactive protein (CRP), increased platelet counts, and low hemoglobin levels. Different epithelial ovarian cancer cell lines are found to produce varying amounts of IL‐6. In this study, a possible relationship between IL‐6 levels in cystic fluids of benign and malignant ovarian tumors and pretreatment serum CRP, platelet counts, and hemoglobin levels was evaluated.

Rising serum values of beta-subunit human chorionic gonadotrophin (hCG) in patients with progressive vulvar carcinomas.

Elevated serum levels of the beta-subunit of human chorionic gonadotrophin (hCG) were measured in 50% of patients with locoregional recurrences or progressive vulvar carcinoma (n = 14). At diagnosis of vulvar cancer, however, the incidence of elevated serum levels was low (5%) in 104 patients. The rising serum levels during progression of disease indicate that the synthesis of the beta-subunit hCG can be increased in vulvar carcinoma.

INHIBIN AS A MARKER FOR GRANULOSA-CELL TUMOR

In order to determine whether serum‐immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo‐oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow‐up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.

Significance of serum SCC antigen as a tumor marker in patients with squamous cell carcinoma of the vulva

The significance of serum SCC antigen as a tumor marker was investigated in 94 women with squamous cell carcinoma of the vulva. The incidence of elevated serum SCC levels varied from 10% in FIGO stage I to 40% in FIGO stage IV. We did not observe a correlation between elevated pretreatment SCC values and the presence of lymph node metastases. During follow-up, elevated serum SCC values were observed in 8 of 19 patients (42%) with recurrent or progressive disease. It is concluded that the determination of serum SCC levels does not provide additional information in the staging of squamous cell vulvar carcinoma, but can be useful for the early detection of recurrent disease during follow-up in some patients. However, elevated serum SCC levels were also found in 25% of patients without demonstrable tumor activity during follow-up and benign skin disorders were recognized as a cause of false-positive SCC results.

Cancer-Associated Antigen CA 195 in Patients with Mucinous Ovarian Tumours: A Comparative Analysis with CEA, TATI and CA 125 in Serum Specimens and Cyst Fluids

The CA 195 levels in ovarian cyst fluids from malignant mucinous tumours (median 2,300,000 U/ml) were significantly higher than the levels in benign mucinous tumours and malignant non-mucinous tumours (medians of 26,800 and 1,700 U/ml, respectively, p = 0.039 and 0.011). Also, the carcinoembryonic antigen (CEA) and tumour-associated trypsin inhibitor (TATI) levels in cyst fluid from mucinous tumours were much higher than those in non-mucinous tumours. Pretreatment serum CA 195 levels were found to be elevated (> 10.5 U/ml) in 72% of the patients with malignant mucinous tumours (n = 25), compared with 35% in malignant non-mucinous tumours and 28% in benign mucinous tumours. The positivity rate shown for serum CA 195 in malignant mucinous tumours was higher than that measured for serum TATI, CA 125 or CEA (60, 53 and 42%, respectively). Measurement of serum CA 195 can be valuable in the clinical management of patients with mucinous ovarian cancer.

Inhibin as a marker for granulosa-cell tumors

In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.