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Antitumor immunity to oral cancer was assessed in 46 patients suffering from squamous cell carcinoma of the oral cavity using a leucocyte adherence inhibition assay (LAI). The response shown by the leucocytes of oral cancer patients to the oral cancer antigen was compared to that shown by the leucocytes from 10 normal age- and sex-matched healthy controls and 43 patients suffering from other types of cancers. Seventy-six percent of the oral cancer patients showed a high degree of leucocyte adherence inhibition in the presence of the antigen. The specificity of this test was further assessed using combinations of the leucocytes from oral cancer patients with extracts from seven cancers occurring at various other sites and extracts of normal oral tissue. The test was highly specific and the leucocytes of oral cancer patients showed significant inhibition only in the presence of oral cancer extract. The inhibition was between 0 and 30% with most other cancer extracts except in the case of extract from cancer of the cervix, where 410 patients showed above 30% inhibition. Specific blocking of the LAI response was observed on addition of sera from oral cancer patients to leucocyte-antigen mixtures from oral cancer patients. This effect was not observed on addition of these sera to specific leucocyte-antigen mixtures from other cancer patients. These observations point towards the usefulness of this test in monitoring antitumor immunity in oral cancer patients.

The clinical validity of using the cancer antigen (CA) 125 — a surface antigen on malignant epithelial ovarian tumors — for diagnosis and follow-up of ovarian cancer was investigated in a cooperative study. Using a monoclonal antibody (OC 125) to detect CA 125, the sera of 850 patients were analyzed by immunoradiometric assay (IRMA-Kit Centocor).

We used an enzyme-linked immunosorbent assay to quantify CA-125, a cancer antigen, in serum of patients with endometriosis. Concentrations of CA-125 in 103 patients with untreated endometriosis significantly (P less than 0.005) exceeded those for 31 controls with no evidence of disease: 9.1 (SD 12.3) vs 2.2 (SD 3.2) arb. units/mL. Values for patients with treated endometriosis were lower (2.3, SD 2.6, arb. units/mL, n = 9) than those for patients with untreated endometriosis. The mean concentrations of CA-125 in different stages of untreated endometriosis were 4.8 (SD 4.5), 7.1 (SD 9.9), 9.8 (SD 13.2), and 10.8 (SD 13.0) arb. units/mL for Stages I, II, III, and IV, respectively. The differences between controls and each stage were statistically significant (for all stages: P less than 0.05). We also assayed serum sampled from controls and patients with untreated endometriosis during menstruation (Group A) and during nonmenstruation (Group B). The efficacy of the present assay for concentrations of CA-125 in serum of patients with endometriosis was greater for Group B than for Group A. Evidently, determination of CA-125 in serum by the present assay may assist in such diagnosis.

Ovarian carcinomas are distinguished by their polyclonality, i.e., heterogeneity and polymorphism of their tissue. There ist no marker available complying with the clinical demands in the case of ovarian carcinoma regarding statisfactory sensitivity and specificity. Therefore, we have simultaneously determined two entirely distinct tumor markers, serum ribonuclease activity (SRA) and cancer antigen 125 (CA 125), recommended in the literature with respect to ovarian carcinoma. After evaluation by logistic regression analysis, we found a specificity of 93% together with a sensitivity of 97% for the simultaneous determination of SRA and CA 125 (37 ovarian carcinomas, 11 cases without pathological findings after treatment, 11 benign tumors of the ovary, 61 controls). The patients are not exposed to increased stress by this simultaneous determination method compared to the determination of a single marker. The increased clinical validity justifies the recommendation of routine simultaneous determinations of SRA and CA 125 for diagnosis and monitoring of patients with ovarian carcinoma.

Sulphoglycoprotein antigens of the foetal alimentary canal have been studied by the immunofluorescence technique, and the presence of sulphomucins demonstrated histochemically from adjacent sections. The material studied consisted of 39 foetuses of between 6 and 16 weeks of gestation. A supplementary autopsy series of newborns was studied by the same techniques. The three sulphoglycoprotein antigens found earlier in normal and pathological adult gastric mucosa appeared between 7 and 8 weeks of gestation and all were present in the foetal alimentary epithelium. The typical location of these antigens showed characteristics either of the normal adult distribution or of the distribution found in pathological conditions in the gastric epithelium. The ca-antigen (cancer antigen) present in cancerous gastric epithelium in adults has now been tentatively named the foetal sulphoglycoprotein antigen (FSA). A comparison is made between the distribution of the sulphoglycoprotein antigens detected by the immunofluorescence technique and that of the sulphomucins seen by histochemical methods. It is suggested that these antigens are mainly situated in sulphated molecules. Les antigenes sulfoglycoproteiniques du tube digestif foetal ont ete etudies par la technique de l'immunofluoresence; l'etude histochimique de coupes voisines a montre la presence de sulfomucines. Le materiel etudie se composait de 39 foetus ǎges de 6 a 16 semaines. On a etudie par les měmes techniques un materiel d'autopsie de nouveau-nes. Les trois antigenes sulfoglycoproteiniques trouves anterieurement dans la muqueuse gastrique normale et pathologique de l'adulte sont apparus entre 7 et 8 semaines de gestation; tous trois etaient presents dans l'epithelium du tube digestif foetal. La localisation typique de ces antigenes presentait soit la distribution de l'adulte normal soit la distribution observee dans les etats pathologiques de l'epithelium gastrique. L'antigene canceereux present dans l'epithelium gastrique cancereux de l'adulte a ete appele provisoirement „antigene sulfoglycoproteinique foetal” (ASF). Une comparaison est etablie entre la distribution des antigenes sulfoglycoproteiniques revelee par l'immunofluorescence et celle des sulfomucines revelee par les methodes histochimiques. Les auteurs considerent que ces antigenes sont situes principalement dans les molecules sulfatees.

Elevated serum levels of several cytokines have been reported in ovarian cancer. We have previously found a diagnostic and prognostic value of hepatocyte growth factor (HGF). The aims of this study were to evaluate the diagnostic and prognostic value of multiple serum cytokines in women with ovarian tumors, and to examine possible associations between serum levels of cytokines and the previously analyzed HGF. Preoperative levels of multiple cytokines were quantified by serum-based immunoassays in 113 women with a pelvic mass: 57 carcinomas, 23 borderline tumors, and 33 benign ovarian tumors. The results were related to clinicopathological parameters. Univariate and multivariate analyses of five-year overall survival were performed. The women with ovarian carcinoma had significantly higher preoperative serum levels of cancer antigen 125 (CA 125), interleukin 8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1) than women with benign ovarian tumors. Serum IL-8 and PAI-1 levels were positively correlated to serum levels of HGF. In a multivariate analysis of five-year overall survival, IL-8 had a prognostic impact. Serum levels of IL-8 and PAI-1 were elevated in women with ovarian carcinoma compared to women with benign ovarian tumors, and positively correlated to serum HGF levels in women with ovarian tumors. IL-8 also seemed to have a prognostic impact.

Carcinoembrionic antigen (CEA) and cancer antigen 125 (Ca125) levels were measured at regular intervals over a 24-month period in 19 patients with proven ovarian cancers. In 91.5% of the cases with recurrent or progressive disease, Ca125 levels were increased whereas only 34% of these patients had increased CEA levels. Furthermore, reduction of the tumoral mass was associated with a decrease of Ca125 levels in all patients. It is proposed that determination of Ca125 levels in ovarian cancer might provide a valuable prognostic tool for the assessment of the evolution of the disease.

From June 1, 1984, to May 31, 1985, 98 cases of epithelial ovarian carcinomas were assessed and followed prospectively using a new murine monoclonal antibody OC 125 which detects the antigen CA 125. Serous tumors comprised 43.7% of cases, mucinous tumors 20.4%, endometrioid tumors 16%, and other epithelial tumors 19.4%. Tumors of low malignant potential and benign epithelial cystadenomas were not included. For this study the upper limit of normal for CA 125 was 20 U/ml. Thirty-six were new cases. In this group the initial CA 125 levels greater than 20 U/ml, greater than 35 U/ml, and greater than 65 U/ml were 97.2, 94.4, and 86.1%, respectively. When mucinous types were excluded the specificity rate did not change significantly. There was no significant difference in initial CA 125 levels between early stages I and II and late stages III and IV. No correlation between tumor bulk and the serum level of antigen was observed. The remaining 62 patients were being followed and in this group 50 were considered to be in remission. Six cases in the remission group had elevated CA 125 levels greater than 20 U/ml and 5 of these developed clinical recurrence. The correlation between the clinical status and concordant fluctuations in the serum levels of CA 125 in all histological types was 87.8 and 93.5% when 10 cases of mucinous tumors were excluded. The contingency coefficient was 0.746. Seven SLOs were performed. All had CA 125 levels less than 20 U/ml and the mean was 6.9 U/ml. Only 1 case was positive with microscopic disease. In our experience CA 125 was invaluable in the management and follow-up of patients with ovarian carcinoma especially for the early detection of recurrent disease and for the monitoring of patients on therapy.

Pleural fluid levels of cancer antigen 125 (CA 125), pancreatic oncofetal antigen (POA), and carcinoembryonic antigen (CEA) were determined in 56 patients with malignant pleural effusion and in 35 patients with tuberculous effusion. Malignant effusions had significantly higher pleural fluid CA 125 and CEA levels than those of tuberculous origin (p less than 0.005). No significant difference in POA titers was found between the two kinds of effusion. Assays of CA 125 and CEA in pleural fluid may be useful in separating malignant from tuberculous effusions. Concurrent measurement of CA 125 and CEA proved superior to determination of CEA alone in discriminating between the two groups.

CA 125 was analysed in serum of 111 patients with ovarian carcinoma. 40 of these patients suffered from manifest cancer, 71 were clinically symptom free after primary treatment of completely resectable disease. Sera from 36 healthy women and 10 patients with benign gyn-disorders served as control. Using a cut-off level of 65 U/ml the evaluation showed a sensitivity of 78% and a specificity of at least 94 % with the exception of benign disorders. Positive rate depended on the amount of tumor burden, grade of clinical tumor activity and histology of the tumors. There was a good discrimination between patients being symptom free after primary treatment and those with manifest disease. Changes in titers reflected the course of the disease.

Serum values of alpha 1-acid glucoprotein (alpha 1-AG) were measured by a radial immunodiffusion technique before the primary operation of 60 ovarian tumors and before the second-look laparotomy of 80 ovarian carcinomas. The results were compared with cancer antigen 125 (CA 125) measurements performed in the same samples by a radioimmunoassay or enzymeimmunoassay. The sensitivity and negative predictive value of the alpha 1-AG measurements were low both before the primary operation (37% and 31%, respectively) and the second-look operation (10% and 51%, respectively). Inversely, the CA 125 measurements before the primary operation demonstrated a sensitivity and negative predictive value of 93% and 81%, respectively. In the second-look group the corresponding CA 125 results were 41% and 62%, respectively. The specificity and positive predictive value of alpha 1-AG before the primary and the second-look operation were high and almost identical to those of CA 125 (93%-100%). All patients with increased alpha 1-AG values also had increased CA 125 levels. Alpha 1-AG cannot be distinguished from immunosuppressive acidic protein (IAP) by radial immunodiffusion technique. In conclusion, the alpha 1-AG analyses did not add new information to the CA 125 measurements. The use of alpha 1-AG (or IAP) as a tumor marker in ovarian cancer cannot be recommended.

The purpose of the present study was to evaluate the information preoperative measurements of cancer antigen 125 (CA 125) may give concerning the nature of an ovarian tumor. Serum samples from 61 patients were analyzed and the results compared with regard to malignancy, FIGO-stage, and histologic type of the tumor. All patients were deemed to have a malignant tumor by clinical examination. Elevated serum levels (greater than 35 U/ml) were found in 44 patients and of these patients 38 had carcinomas, 5 had borderline tumors, and one had a benign tumor (false positive). Normal serum levels (less than or equal to 35 U/ml) were registered in 17 patients. Fourteen of these had benign tumors and 3 had malignant (false negative). The false positive sample and the 3 false negative samples observed in the present study result in a positive and negative predictive value of the CA 125 analysis of 98% (43/44) and 82% (14/17) respectively. The positive predictive value of the clinical examination was 75% (46/61). It is concluded that measurement of CA 125 is a valuable adjunct to the preoperative examination of patients with ovarian tumors.

A case of primary retroperitoneal cystadenocarcinoma is presented as the fourth reported case in the world literature to date. The cyst was removed intact and demonstrated an infiltrating malignant process with nuclear pleomorphism and mitotic activity. No ovarian tissue was identified and a cancer antigen 125 (CA 125) test was normal. The patient underwent a staging procedure subsequently that included peritoneal washings, hysterectomy, bilateral salpingoophorectomy, and iliac node dissection. No metastases were found and the patient is without recurrence 22 months postoperative. The literature is reviewed to better define the origin and prognosis of these tumors.

In order to evaluate the diagnostic yield of tumor markers in differentiating malignant and benign pleural effusions, we carried out a prospective study in a group of Iranian people. Pleural and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3), neuron-specific enolase (NSE) and cancer antigen 125 (CA 125) were assayed prospectively in patients with pleural effusion (40 malignant and 37 benign). The highest sensitivity was obtained with a combination of CA 15-3 in serum, and CA 15-3 and CEA in pleural fluid (80%), also with combination of CA 15-3 in serum, and CA 15-3, NSE and CEA in pleural fluid (80%). The highest specificity was obtained with combination of CA 15-3 in serum, and CA 15-3 and NSE in pleural fluid (100%), and also with combination of CA 15-3 in serum, and CA 15-3, NSE and CEA in pleural fluid (100%). (Pathology Oncology Research Vol 11, No 4, 236–241)

Genome-wide gene expression profile analyses revealed that Ras and EF-hand domain containing (RASEF) was significantly transactivated in the majority of lung cancers. Transient expression of RASEF promoted cell growth, whereas transfection of siRNA for RASEF to lung cancer cells reduced its expression and resulted in growth suppression of the cancer cells. Immunohistochemical staining using tumor tissue microarrays consisting of 341 archived non-small cell lung cancers revealed the association of strong RASEF positivity with poor prognosis (P = 0.0034 by multivariate analysis). RASEF could bind to extracellular signal-regulated kinase (ERK) 1/2 and appeared to enhance the ERK1/2 signaling. In addition, inhibition of interaction between RASEF and ERK1/2 using cell-permeable peptide that corresponded to the ERK1/2-interacting site of RASEF protein, suppressed growth of lung cancer cells. RASEF may play important roles in lung carcinogenesis, and could be useful as a prognostic biomarker and a target for the development of new molecular therapies.

Serum cancer antigen 125 was measured in subjects with intrauterine pregnancy (n = 44), ectopic pregnancy (n = 76) and in nonpregnant controls (n = 17). Values were appreciably elevated only in ruptured tubal gestations.

In a recent paper published in conjunction with Dr. W. S. Thomas, 1 I have pointed out that the blood serum of cancer patients may contain a substance or substances which, in the presence of cancer extract, will bind a larger amount of complement than the blood serum of normal individuals. It was found that this reaction could be obtained in about 65 per cent, of the cancer cases, while it was absent in 98 per cent, of our non-cancerous patients and in all normal persons. The small number of positive results in non-malignant cases finds its probable explanation in the fact that cancer antigen may react with the blood serum of syphilitic individuals and thus likewise bring about an abnormal degree of complement fixation. Our paper was sent to the Journal of Experimental Medicine early in May, and we were hence unable to notice certain papers bearing on the