Study on the plasma plasminogen activators in patients with malignant gynecologic tumors

Increased plasminogen activator (PA) secretion has been observed in malignant cells and tissue and PA is thought to be involved in the processes of tumorigenesis, cancer invasion and metastasis. Recently two types of plasminogen activator--tissue type PA(tPA) and urokinase type PA(uPA)--have been detected in human plasma. In this study, to investigate the relationship between circulating PA and the malignant state, we measured the plasma PA concentrations (PA activity, tPA and uPA antigen) in 69 women with gynecologic malignancies (cervical cancer 50, ovarian cancer 19). These concentrations were compared to those in control groups of 33 women with benign gynecologic tumors (uterine tumor 8, ovarian tumor 25). An enzyme-linked immunoassay for tPA and uPA antigens was performed by the modified method described by Takada et al. (1986). PA activity was measured by the sensitive spectrophotometric assay of Verheijen et al. (1982). The blood samples were taken from an arm vein with a minimum of venous occlusion before treatment. There was no correlation between PA activity or uPA antigen levels and the malignant state. However, in the case of uterine tumors, a significantly higher concentration of tPA antigen (10.5 +/- 5.1 ng/ml) was found in patients with cervical cancer, in stage IV, than in those in the benign group (5.2 +/- 2.0 ng/ml). Moreover the tPA antigen concentration in cervical cancer, stage IV, was higher than in stages 0-III.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of D-dimer in diagnosis of ovarian cancer

One of fibrin degradation products, D-dimer was measured in ovarian cancer (N = 28), benign ovarian tumors (N = 26), benign uterine tumors (N = 15) and normal controls (N = 66). The D-dimer value for ovarian cancers was 721 +/- 423 ng/ml, benign ovarian tumors; 299 +/- 248, benign uterine tumors; 248 +/- 141, and normal controls; 237 +/- 212, respectively. There was a significant difference between the ovarian cancer group and the other groups (p less than 0.01). When the cut off level of D-dimer was less than 400 ng/ml, the positive rate for D-dimer was 50% in stage I of ovarian cancer, 88% in stage II, 86% in stage III and 80% in stage IV. Overall, 82% of ovarian cancer patients were positive. D-dimer provides good sensitivity compared with other ovarian cancer markers such as TPA, SLX and CEA. The coefficient correlation between D-dimer and CA125, TPA, SLX or CEA was 0.476, 0.376, 0.226, -0.292, respectively. This suggest that the measurement of D-dimer is useful in diagnosing ovarian cancer.     

The clinical significance of tissue polypeptide antigen (TPA) in the patients with gynecologic tumor

In order to estimate the clinical significance of tissue polypeptide antigen (TPA), TPA was measured by radioimmunoassay in sera from patients with various gynecological tumors. They were 40 uterine myomas, 94 cervical cancers, 21 endometrial cancers, 3 vulval cancers, 51 benign ovarian tumors and 78 malignant ovarian tumors including 18 low potential malignant tumors (LPM). The mean TPA values in patients with benign as well as malignant tumors were significantly higher than that of 97 healthy volunteers (68 +/- 17 U/l; Upper limit; 107 U/l). Among the cervical cancer patients, serum TPA level and positive ratio became higher as the disease progressed. In the advanced cases, the mean serum TPA value and positive ratio were 149 +/- 64 U/l and 75%, respectively. The mean TPA value in the endometrial cancer patients was significantly higher than that of myoma patients. Among the patients with ovarian tumor, serum TPA was elevated in 14% of benign cases, 28% of LPM cases, 47% of stage I cases and 82% of the advanced cases. Serum TPA values varied directly with the stage and malignancy of disease. The present study revealed that TPA is a useful markers in the diagnosis of gynecological tumors, especially for ovarian cancers.     

Clinical significance of sialic acid determinations in patients with gynecologic cancer

Sialic acid (SA) levels were measured in human sera by the enzymatic procedure using neuraminidase. Sera were obtained from healthy controls (70 females), patients with uterine myoma (27 cases), cervical cancer (53 cases), benign ovarian tumor (36 cases) and ovarian cancer (70 cases). The upper normal limit of 72mg/dl was obtained from the mean +2SD for healthy controls. The mean value for serum SA in patients with primary ovarian cancer (71.2 +/- 20.6mg/dl) was statistically higher than those for both uterine myomas (59.0 +/- 12.4mg/dl) and controls. The mean level for SA in patients with ovarian cancer was further elevated and it was statistically higher than that for benign ovarian tumors (58.8 +/- 14.3mg/dl), uterine myomas and cervical cancers. SA levels were not well correlated with tumor histologic types or clinical stages of cancer patients. As to the relationship between SA and the clinical course of cancer patients, changes in SA values were well correlated with the curability of tumor resection. The lack of specificity, however, will require careful interpretation of the SA value to assure that inflammation is not causing changes in the test values, because SA shows a transient increase due to the inflammatory reaction during the postoperative period even in patients with benign tumor. These results indicate that SA determination is highly recommended as an addition to the conventional diagnostic methods.     

Management of patients with gynecologic cancer by serum sialic acid determination

With an enzymatic technique, serum sialic acid (SA) levels were determined in patients with gynecologic tumors. Since the SA level for healthy females was 57.4 +/- 7.3 mg/dl, we set the upper normal limit of this parameter at 72 mg/dl. The SA level became larger in ascending order of uterine myoma, benign ovarian tumor, cervical cancer, corpus cancer, and ovarian cancer. The SA level proved to be significantly higher in cancer patients showing poor prognosis than in those having good prognosis irrespective of the category of therapy and it reflected well the clinical course of cancer patients. In patients who receive a combination therapy and need to be followed up for a long term, complete follow-up is sometimes impossible with tumor-derived markers alone. Even in such cases, the sialic acid level will work as a useful follow-up marker because it is nonspecific to histologic types of cancer.     

Macrophage-colony stimulating factor and ovarian cancer]

BACKGROUND: In this study the use of macrophage-colony stimulating factor (M-CSF) as tumor marker for ovarian cancer is evaluated. METHODS: Serum samples were obtained from 74 patients, 43 of these were affected by ovarian carcinoma and 31 by benign ovarian tumors. The M-CSF levels were assayed with an ELISA method and compared with those of 148 healthy women. CA 125 levels were also evaluated. RESULTS: In healthy women the M-CSF levels were 770.4 +/- 145.9 U/ml, the upper limit of normal level was considered 1056 U/ml. Serum M-CSF levels were significantly high in patients with ovarian cancer (1425.3 +/- 1007.1 U/ml; p < 0.001) and in 29 of the 43 patients exceeded the limit of 1056 U/ml. No differences were observed among the histologic types. There were no significant differences between patients with benign ovarian pathology and healthy women. No definite relationship was found with CA 125, but evaluating at the same time M-CSF and CA 125 positive results were found in 95.3% of cases. CONCLUSIONS: Therefore M-CSF can be considered a marker for ovarian cancer, and the assay of its serum levels can be particularly useful in association with those of CA 125.     

Diagnostic value of telomerase activity in gynecologic malignancies

Nagai N, Murakami J, Oshita T, Ohama K, Tahara H. Diagnostic value of telomerase activity in gynecologic malignancies. Int J Gynecol Cancer 1998; 8 : 481–488.
We investigated the diagnostic significance of telomerase activity in gynecological malignancies. Tissue samples were obtained from 24 cervical cancers, 27 uterine cancers (22 endometrial cancers and five sarcomas), 33 ovarian cancers (31 epithelial tumors and 2 germ cell tumors), and 11 benign ovarian tumors. In addition, cervical cytology specimens were obtained from 30 squamous intraepithelial lesions (13 low grade and 17 high grade), and from 22 normal females. Telomerase activity was detected using the TRAP assay, and the relative telomerase activity was obtained using the BioMax DNA image analysis system. Telomerase activity was detected in 22/24 (91.7 %) cervical cancers, 23/27 (85.2%) uterine tumors and 30/33 (90.9%) ovarian cancers. Weak telomerase activity was detected in two mature cystic teratomas and also found in 9/17 (52.9%) high grade SIL and 2/13 (15.4%) low grade lesions. Telomerase activity showed no relationship with tumor histology or clinical stage, and there was no statistically significant difference between patients with uterine cancer and ovarian cancer. Relative telomerase activity showed a correlation with the dilution assay, and significantly higher telomerase activity was found in uterine cervical cancer compared with precancerous lesions and in ovarian cancer compared with benign ovarian tumors. After establishment of an assay for telomerase, it may be useful for cancer diagnosis and identification of high-risk groups.     

Clinical evaluations of the tumor marker sialyl SSEA-1 antigen for clinical gynecological disease

Sialyl SSEA-1 antigen (SLX) is a highly specific tumor marker composed of sugar chain antigens that have Lewis X at their terminals and bind to sialic acid. This antigen is rarely detected in normal tissues, and is present in adenocarcinoma and fetal tissues. We studied the clinical usefulness of SLX in gynecological patients and obtained the following results. (1) The antigen was frequently positive in patients with ovarian cancer with a mean of 89.5 +/- 48.3 U/ml (72.8%, 8/11) and in those with endometriosis with a mean of 39.8 +/- 10.3 U/ml (75.0%, 6/8). (2) Among the gynecological malignancies, the percent positivity was low in those with cervical cancer (20.0%, 5/25), endometrial cancer (33.3%, 1/3), and cancer of the fallopian tube (33.3%, 1/3). (3) The antigen was negative in 20 with myoma uteri, 20 normal pregnant women, and 9 nonpregnant healthy women during the follicular, luteal, or menstrual phase. It was negative in 8 of 9 patients with benign ovarian cyst. False negative results were rare. (4) The SLX level was higher in the ascites than in the serum in patients with ovarian cancer and in those with benign ovarian tumors. (5) The serum SLX in patients with ovarian cancer, which was positive before tumor resection, became negative 2 weeks postoperatively. These results suggest that SLX is a tumor marker with a high specificity to adenocarcinoma of the reproductive organs.     

Transvaginal color Doppler imaging for hemodynamic assessment of reproductive tract tumors.

Transvaginal color Doppler flow imaging was carried out on 68 Japanese women (normal, 10; uterine myoma, 21; cervical carcinoma, 7; endometrial carcinoma, 10; benign ovarian tumor, 12; ovarian carcinoma, 8). Blood flow velocity waveforms were evaluated by calculation of the resistance index (RI). In 6 patients with cervical carcinoma neovascularization was evident within the cervix. In all patients with endometrial carcinoma such signs were present adjacent to and/or within the endometrium. These findings were absent in normal women and in those with myomata. There was a significant difference between the RI (0.510 +/- 0.097) in patients with cervical carcinoma and in normal women (0.881 +/- 0.048) in the ascending branch. In endometrial carcinoma the RI (0.535 +/- 0.158) was significantly lower in the arcuate artery compared to the normal uterus (0.768 +/- 0.075) and patients with uterine myoma (0.679 +/- 0.131), respectively. There was no area of neovascularization in the normal ovaries. Neovascularization was confirmed in four patients with a benign ovarian tumor and in all patients with an ovarian carcinoma. A significantly lower RI was obtained in cases of ovarian carcinoma (0.503 +/- 0.122) than in patients with benign ovarian tumors (0.888 +/- 0.216). Transvaginal color Doppler imaging and pulsed Doppler analysis may be useful diagnostic tools to differentiate benign and malignant tumors.     

Clinical significance of new tumor marker CA 125 in gynecological cancer--particularly usefulness in diagnosis of ovarian cancer

A concentration in sera of a new antigen CA125 related to cancer of the ovary was measured by radioimmunoassay which used a monoclonal antibody, and its usefulness as a tumor marker in the diagnosis of cancer of the ovary was investigated. The mean values for CA125 in sera of healthy controls (80 females) were 14.2 +/- 12.2 U/ml. Mean values for CA125 in sera of various patients were 29.0 +/- 39.6 for myoma uteri (30 cases), 26.7 +/- 30.1 for benign ovarian tumors (10 cases), 64.4 +/- 146.2 for cervical carcinoma (14 cases), and 31.5 +/- 19.8 for endometrial carcinoma (6 cases), whereas the mean values for ovarian cancers (23 cases) were as high as 311.3 +/- 250.4. On the other hand, positive rates for CA125, when the cut-off value was set to 65 U/ml, were 1.3% for healthy controls (1 out of 80 cases), 10.0% for myoma uteri (3 out of 30 cases), 10.0% for benign ovarian tumors (1 out of 10 cases), 14.3% for cervical carcinoma (2 out of 14 cases), and 16.7% for endometrial carcinoma (1 out of 6 cases), whereas the positive rate for ovarian cancers was 78.3% (18 out of 23 cases). Especially for serous cystadenocarcinoma, the positive rate was 100% (10 out of 10 cases). From the above, the measurement of CA125 in sera was considered to be significant in the diagnosis of ovarian cancer.     

卵巢恶性肿瘤患者测定血清血管内皮生长因子的临床价值

目的　探讨血清血管内皮生长因子 (VEGF)测定对卵巢恶性肿瘤诊断、病程监测和预后的价值。方法　采用酶联免疫吸附法 (ELISA)对 90例健康妇女 (对照组 )、2 5例卵巢良性肿瘤 (良性组 )及 12 0例卵巢恶性肿瘤 (恶性组 )进行血清VEGF含量分析 ,并进一步对其中 2 5例卵巢恶性肿瘤患者进行手术治疗前后血清VEGF含量的动态观察。结果　 ( 1)恶性组术前血清VEGF含量为 ( 766±12 3 7)mg/L ,显著高于良性组的 ( 5 6± 2 3 )mg/L及对照组的 ( 5 5± 19)mg/L(P =0 0 0 6) ,以 10 0mg/L为界值 ,其诊断的特异性为 87% ,敏感性为 77% ;( 2 )恶性组临床分期Ⅰ～Ⅱ期和高～中分化患者术前血清VEGF含量分别为 ( 198± 2 87)mg/L和 ( 2 80± 5 5 2 )mg/L ,明显低于临床分期Ⅲ～Ⅳ期的 ( 95 5±1716)mg/L和低分化患者的 ( 991± 13 49)mg/L (P <0 0 5 ) ;但血清VEGF含量与组织学类型无关 (P>0 0 5 ) ;( 3 )手术治疗后血清VEGF含量为 ( 118± 110 )mg/L ,较手术治疗前血清VEGF含量 [( 10 74±12 11)mg/L]明显下降 ;( 4)初治患者血清VEGF阳性者 (即VEGF≥ 10 0mg/L)平均总生存期为 2 8个月 ,而血清VEGF阴性者平均总生存期为 3 5个月 (P <0 0 5 )。但COX模型分析结果发现 ,VEGF不是与卵巢恶性肿瘤预后相关的独立因素 (P     

CA 125 in gynecologic practice

Serum CA 125 levels were determined in 64 women with benign ovarian lesions, 92 women with uterine fundal lesions, and six patients who had negative second-look laparotomy for epithelial ovarian carcinoma. Of those with benign lesions, 13 of 31 patients with endometriosis had levels greater than 35 U/ml. Six of 34 patients with endometrial carcinoma had elevated levels before the primary operation, and six of 15 patients with recurrent endometrial carcinoma had elevated levels. The six ovarian cancer patients had had negative findings at second look 7 to 40 months before recurrence. Where close serial levels were available, the level became elevated 2 to 5 months before clinically apparent recurrent disease was noted.     

Interleukin-7 and suppression of local peritoneal immunity in ovarian carcinoma.

OBJECTIVES: To investigate the epithelial ovarian carcinoma (EOC) secretion of interleukin-7 (IL-7). METHODS: Levels of IL-7 were assayed by enzyme-linked immunoadsorbent assay and IL-7 mRNA, and protein expression in tissues and cell lines were detected by RT-PCR and immunohistochemistry. RESULTS: The median serum IL-7 level in patients with EOC (32 cases; 32.49 pg/ml) was significantly higher than that of patients with benign tumors (16 cases; 7.59 pg/ml) and healthy women (16 cases; 10.64 pg/ml) (P<0.05). The median peritoneal fluid IL-7 level in patients with EOC (17.39 pg/ml) was slightly higher than that of patients with benign tumors (14.09 pg/ml), but not significantly so (P>0.05). There were positive correlations between the serum and peritoneal fluid IL-7 levels in both ovarian cancer and benign group (P<0.05, both). Only two EOC specimens expressed IL-7 mRNA, and no IL-7 protein positive was found in any specimens. CONCLUSIONS: Epithelial ovarian carcinoma cells rarely express IL-7, and IL-7 levels are decreased in the ascitic fluid of patients with EOC.     

Analysis of CA 125 assay system and its diagnostic significance in gynecologic tumors

CA125 antigen levels were measured in patients with ovarian cancer (54 cases) by the RIA method using a monoclonal antibody OC125 and were examined as a marker for ovarian cancer. The upper normal limit of CA125 of 35 U/ml was derived from the mean value (15.7 U/ml)+2SD (9.3 U/ml) of CA125 in healthy controls. The mean value for CA125 in patients with ovarian cancer (1160 +/- 1850 U/ml) was statistically (p less than 0.001) higher than those of healthy controls, benign ovarian tumors (28 +/- 20 U/ml) and cervical cancers (226 +/- 526 U/ml). Elevated CA125 levels were also found in the early pregnant stage and endometriosis, but these cases showed not so high CA125 values as those of ovarian cancers. In addition, CA125 levels were not clearly affected by the menstrual cycle. Among ovarian malignancies, the elevated CA125 values were specifically demonstrated in serous cystadenocarcinoma (positivity 89%) and markedly low in mucinous cystadenocarcinoma (positivity 16%). No positive correlation of CA125 values with the clinical stage (FIGO) were found in any ovarian cancer patients. The rise and fall of CA125 levels corresponded closely with progression and regression of cancer patients with positive CA125 levels. In conclusion, serum CA125 determinations may be useful in patients with ovarian cancer (except for mucinous type) for diagnosis and for monitoring the results of the treatment.     

A study on tumor marker of tissue-polypeptide-antigen (TPA) in gynecologic malignancies

Tissue polypeptide-antigen (TPA), a tumor-associated antigen reported by Bjorklund et al., is a single chain polypeptide of approximately 22,000-45,000 molecular weight, which is being studied in various fields as a tumor marker. We determined the serum TPA level and tissue distribution of TPA in patients with gynecologic malignancies and healthy women. In healthy women, the serum TPA level was under 110 mu/l, without any relation to age or sex. In benign tumors, the mean serum TPA was 123.9 mu/l and it is comparable with that in healthy women. In cervical cancers, it was 212 mu/l and significantly higher than those in healthy women and in patients with benign tumors (p less than 0.01). In ovarian cancers, it was 414.7 mu/l, which showed significantly higher levels of serum TPA in ovarian cancers than those in healthy women and in patients with benign tumor, and it was also significantly higher than that in cervical cancers (p less than 0.001). As for the values after treatment, the serum TPA level clearly tended to fall in patients exhibiting good response, and tended to rise in those showing poor response. TPA was markedly localized in the cancer cells, but was almost entirely absent from the normal tissues of the cervix and endometrium.     

The activity of cancer procoagulant in cases of uterine leiomyomas

PURPOSE: It is currently believed that cancer procoagulant (CP), an enzymatic protein, is a product of malignant neoplastic cells. The present study was designed to test whether it is also synthesized by benign neoplastic cells, namely uterine leiomyomas. MATERIALS AND METHODS: We determined the activity of CP in the blood serum of women with uterine leiomyomas (N = 24), normal women (N = 15), and genital cancer patients (N = 6) by the coagulative method according to Gordon and Benson. Also, the CP activity in 10% tissue homogenates of uterine leiomyomas, normal uterine muscle and tissues of cervical and endometrial carcinoma was determined by the chromogenic method according to Colucci et al. RESULTS: The mean CP activity in the sera of women with uterine leiomyomas was 181.1 seconds (s) +/- 19.9 s, in healthy women--293.2 s +/- 33.8 s, and in genital cancer patients--78.8 +/- 18.5 s (all differences: p < 0.001). Similarly, in homogenates of uterine leiomyomas the CP activity was 19.6 +/- 3.8 nmoles pNa/ml, in normal uterine muscle it was 13.2 +/- 2.2 nmoles pNa/ml, and in cancerous tissue--28.0 +/- 6.6 nmol pNa/ml (all values being significantly different from each other). There was a strong correlation (r = -0.8122; p < 0.001) between the CP activity in uterine leiomyomas and serum activity, suggesting that the source of the serum CP activity was from the leiomyoma. The coagulation time of 120 to 240 s by the Gordon and Benson method supported the diagnosis of uterine leiomyoma, and a value below 120 s--the suspicion of genital cancer. CONCLUSIONS: Uterine leiomyomas, representing benign genital neoplasia, synthesize CP and are the likely origin of CP activity in blood, as has been described for malignant tumors, but to a lesser degree. There may be a role for CP as a tumor marker of genital neoplasia.     

Assessment of soluble intracellular adhesion molecule-1 (sICAM-1) in women with benign ovarian tumors

OBJECTIVES: Overexpression of intracellular adhesion molecule-I (ICAM-1) was observed in many benign and malignant tumors. The aim of our study was to evaluate its serum concentrations as well as CA-125 in women with benign ovarian tumors. MATERIALS AND METHODS: Forty-five women treated surgically because of benign ovarian mass. RESULTS: Mean concentrations of sICAM-1 in benign tumors was 241.8+/-74.1 ng/ml and 195.6+/-68.7 ng/ml in healthy controls. No correlations between sICAM-1 concentrations and leukocyte count, tumor volume, BMI and obstetrical history. Efficiency in tumor differentiation was higher for CA-125 than sICAM-1 (area under Receiver Operating Characteristic curve 0.78 and 0.63 respectively). We observed higher sICAM-1 concentrations in fibrothecomas and lower in endometrial and dermoid cysts. CONCLUSIONS: Serum ICAM-1 concentrations correlate with some histological types of benign tumors, but not with tumor volume. Levels of CA-125 are more effective than ICAM-1 in ovarian tumors differentiation.     

Differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis by a combination assay of serum sialyl SSEA-1 antigen and CA125 levels

We used a combination assay of serum sialyl SSEA-1 antigen (SLX) and CA125 levels, and evaluated the clinical usefulness of this technique for a differential diagnosis of ovarian cancer, benign ovarian tumor and endometriosis. In 82 patients with ovarian tumors, the sera of 20 (64.5%) of 31 with ovarian cancer and 15 (48.4%) of the 31 with endometriosis (endometrial cyst) were positive for both SLX and CA125, but serum SLX level was 5 U/ml or less in these 14 SLX- and CA125-positive patients with endometriosis. The sera of 16 (80.0%) patients with benign ovarian tumor were negative for both tumor markers. The sera of 3 (9.7%) of 31 with ovarian cancer and the sera of 2 (6.5%) of 31 with endometriosis were negative for both markers. The diagnostic accuracy (true positive rate X true negative rate) of the combination assay for ovarian cancer was 49.0% when the cutoff value of the serum SLX was 38 U/ml but improved to 78.5% when the value was set at 50 U/ml. When the cutoff value of serum SLX was set at 50 U/ml and that of serum CA125 at 35 U/ml, 27 of 37 patients who were positive only for CA125 had endometriosis. From the above observations, a combination assay of serum SLX and CA125 is a promising method for the differential diagnosis of malignant and benign ovarian tumors. Our results also suggest that to improve the diagnostic accuracy, the cutoff value of the serum SLX level should be 50 U/ml for ovarian tumors alone.     

Significance of immunosuppressive acidic protein in the diagnosis and follow-up of patients with ovarian cancer, in particular as a marker for chemotherapeutic effects

Serum immunosuppressive acidic protein (IAP) was determined in patients with ovarian cancer and was examined as a marker for ovarian cancer when, chemotherapy in particular, was applied. Samples were sera obtained from 68 ovarian cancers, 74 benign ovarian tumors, 54 cervical cancers, 57 uterine myomas and 88 healthy controls. Elevated levels of IAP were found in 89.5% of patients with ovarian cancer and this high positive ratio was not affected by tumor histologic features. The measurement of the serum IAP level is useful for the initial diagnosis of ovarian cancer because of low false positive rates (8.1%) in benign ovarian tumors and high positive rates even in the early stage of ovarian cancer. Serial determinations of serum IAP levels were well correlated with the response to the treatment (chemotherapy in particular) and the prognosis of cancer patients, even in the case of patients with leucocytopenia induced by the intensive chemotherapy. In case of recurrent patients (whose lesions were observed in the intraperitoneal space), IAP values tended to increase earlier than other conventional tumor-derived markers. Therefore, IAP may also be a useful follow-up marker for patients with ovarian cancer (particularly, for the early detection of recurrence).     

The significance of serum leucine aminopeptidase (P-LAP) determination in the gynecological malignancies

We determined Placental-Leucine Aminopeptidase (P-LAP) activity, one of the oncodevelopmental antigens, in sera and in tissues of patients with gynecological cancers. The incidence of P-LAP activity and clinical usefulness of the determination of serum P-LAP activity were studied. The mean level in healthy non-pregnant sera used as controls was 6.0 +/- 2.4mg/dl/h. The mean level of P-LAP activity in patients with benign tumors such as myoma uteri and benign ovarian tumor did not increase in comparison with the controls. The mean level of P-LAP activity in patients with malignant tumor increased with advancing stages, and especially in advanced cervical and ovarian cancer, serum P-LAP levels were significantly higher than in the controls. Serum P-LAP activity correlated with the serum ferritin concentration (r=0.613), but not with the serum alpha-fetoprotein and serum carcinoembryonic antigen concentration. Serial measurements of serum P-LAP activities in patients with gynecological cancer showed that serum P-LAP activity might reflect the progress of cervical and ovarian cancer. Tissue P-LAP activities in 29 ovarian cancers were compared with those in normal tissues. Tissue P-LAP activities in 26 cases out of 29 increased to twice as high as the mean activities in 10 normal ovaries. Our present results suggest the possibility of using P-LAP activity as one of tumor markers for gynecological malignant tumors.