Tumour-associated trypsin inhibitor (TATI) and cancer antigen 125 (CA 125) in mucinous ovarian tumours

A tumour-associated trypsin inhibitor (TATI) and the cancer antigen 125 (CA 125) were measured pre- or peroperatively in 30 patients with mucinous ovarian tumours (10 malignant, two borderline and 18 benign) to investigate the separate and combined use of the two markers as a diagnostic tool. In the malignant and borderline cases considered as a whole, TATI was elevated in 83% and CA 125 in 50%. The former marker was increased in one (6%) benign tumour and the latter in another (6%). The combined use of TATI and CA 125 ensured diagnosis of all malignant and borderline tumours. The specificity was 89% and the positive predictive value 86%. In conclusion, in the distinction of malignant and borderline mucinous ovarian tumours from benign ones TATI was a more reliable tumour marker than CA 125. The combined use of TATI and CA 125 ensured diagnosis of all malignant and borderline tumours in the present series.     

Explanation of the limited correlation between tumor CA 125 content and serum CA 125 antigen levels in patients with ovarian tumors

The concentration of the tumor marker CA 125 in tumor tissue, cyst fluid, ascites fluid, and serum from patients with epithelial ovarian tumors was quantitated. Immunohistologic studies showed that CA 125 was present in 90% of the nonmucinous epithelial ovarian tumors. Quantitative analysis of the fluid from 57 cysts revealed that CA 125 was present in concentrations of up to 2140,000 U/ml in samples from malignant nonmucinous epithelial ovarian lesions, and up to 116,000 U/ml in mucinous tumors, but also in concentrations of up to 371,000 U/ml in benign serous cystadenomas. In contrast, pre-operative serum CA 125 levels were elevated in almost all of the patients with malignant ovarian tumors but not in most of those with benign ovarian tumors. These findings suggest that in benign ovarian tumors there is an effective barrier between the cyst fluid and the circulation that prevents the appearance of CA 125 in the serum, whereas in malignant tumors infiltrative growth leads to the release of antigen into the circulation. Furthermore, CA 125 values in ascites fluids were up to 130 times higher than the serum antigen levels, which indicates that the peritoneum serves as a barrier for high molecular weight tumor antigens. The current results show that tumor basement membranes and peritoneal barriers play a notable role in the transit of tumor antigens, one which must be taken into account in the monitoring of serum marker levels of cancer patients.     

TATI (tumour-associated trypsin inhibitor) as a marker of ovarian cancer.

In ovarian cancer patients a 6 kDa polypeptide, the tumour-associated trypsin inhibitor (TATI), can occur at elevated concentrations in both urine and serum. In this study pretreatment serum levels of TATI (cut-off point 21 ng ml-1) and CA 125 (cut-off points 35 U ml-1 and 65 U ml-1) were determined in 152 patients with epithelial ovarian cancer (115 primary and 37 recurrent) and in 267 women with benign pelvic diseases. The data obtained were correlated with the tumor stage, histological type and tumour grade. Overall, TATI showed a sensitivity of 64% and a specificity of 75%. The sensitivity and specificity of CA 125 > 35 U ml-1 were both 80%. Corresponding values for CA 125 > 65 U ml-1 were 70% and 87%. The combination of the two markers increased the sensitivity to 91% (CA 125 > 35 U ml-1) and 86% (CA 125 > 65 U ml-1), while the specificity dropped to 61% and 68% respectively. TATI was clearly superior in mucinous carcinomas of the ovary, the rate of true-positive findings in these neoplasms was 67% vs 42% for CA 125 > 35 U ml-1 and 33% for CA 125 > 65 U ml-1. Unlike CA 125, TATI correlated well with tumour grade. The combination of the two markers had a higher negative predictive value, i.e. 93% (CA 125 > 35 U ml-1) and 90% (CA 125 > 65 U ml-1) respectively. It is concluded that, while TATI cannot replace CA 125 in the diagnosis of malignant epithelial carcinomas of the ovaries, it is a valuable additional marker in cases of mucinous carcinomas and in combination with CA 125.     

Comparative analysis of CA125, tissue polypeptide specific antigen,and soluble interleukin-2 receptor alpha levels in sera,cyst, and ascitic fluids from patients with ovarian carcinoma

BACKGROUND: The serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin-2 receptor alpha (sIL-2Ralpha) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms. METHODS: CA125, TPS, and sIL-2Ralpha concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms. RESULTS: CA125, TPS, and sIL-2Ralpha levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III-IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I-II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL-2Ralpha). Concurrent measurement of CA125 and sIL-2Ralpha in sera identified 100% of ovarian carcinomas in FIGO Stage I-II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL-2Ralpha was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III-IV disease compared with patients who had FIGO Stage I-II disease (P = 0.002), whereas such correlations were not found for TPS or sIL-2Ralpha. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL-2Ralpha levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL-2Ralpha levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms. CONCLUSIONS: In patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL-2Ralpha values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL-2Ralpha levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers.     

Tumour-associated trypsin inhibitor (TATI) in ovarian cancer

Tumour-associated trypsin inhibitor (TATI) is a 6 kD peptide isolated from the urine of a patient with ovarian cancer. Increased urinary excretion of TATI has earlier been observed in patients with gynaecological malignancies. The value of TATI in urine and serum as a marker for ovarian cancer was studied in 102 patients. Preoperatively urine TATI was elevated in 55% (18/33) and serum TATI in 27% (12/45) of the patients. In patients with mucinous tumours, elevated preoperative levels of TATI were observed in 6 out of 10 patients, while CA 125 was elevated in 4 and CEA in one of the cases. When assay of TATI was used to predict presence of disease before second-look surgery of 48 patients, the sensitivity and specificity of serum TATI was 19% and 91%, and that of urine TATI 42% and 76%, respectively. Rising TATI levels were observed in progressive disease, whereas regressive disease was not as often associated with falling levels. Serum TATI was elevated in 45% (144/318) and urine TATI in 57% (73/171) of samples from patients with clinical evidence of disease. The TATI assay was found to be of potential value in the management of patients with mucinous ovarian cancer, but in patients with non-mucinous ovarian cancer it did not provide information additional to that obtained from assay of ovarian cancer marker CA 125 alone.     

Cyst fluid of ovarian cancer patients contains high concentrations of trypsinogen-2

We have determined the concentrations of two tumor-associated trypsinogen (TAT) isoenzymes, called TAT-1 and TAT-2, in human ovarian tumor cyst fluid using monoclonal antibody-based immunofluorometric assays specific for each isoenzyme. TAT-1 and TAT-2 are immunologically indistinguishable from the two pancreatic trypsinogen isoenzymes, cationic trypsinogen (-1) and anionic trypsinogen (-2). Our results show that of the two isoenzymes TAT-2 is the predominant form in cyst fluid and its concentrations are significantly higher than the levels of the trypsinogen isoenzymes in serum and in preovulatory follicular fluid from hyperstimulated ovaries. The median concentration of TAT-2 was higher in mucinous than in serous cyst fluid as has been found previously for the specific trypsin inhibitor, tumor-associated trypsin inhibitor. Most notably, in mucinous cyst fluids the median level of TAT-2 was higher in borderline and malignant (2640 micrograms/liter) than in benign cases (84 micrograms/liter). Also in serous cyst fluids the TAT-2 level was higher in borderline and malignant (median 345 micrograms/liter) than in benign cases (median 18 micrograms/liter). In fluids from other types of malignant ovarian carcinomas slightly elevated levels of TAT-2 were also observed (median 62 micrograms/liter). The identity of the trypsinogens was verified by isolating them by immunoaffinity chromatography using monoclonal antibodies. The increased levels in association with malignancy suggest that TAT is involved in ovarian tumor dissemination and breakage of tissue barriers.     

Diagnostic significance of the tumour markers CEA, CA 15-3 and CA 125 in malignant effusions in breast cancer

Concentrations of the tumour-associated antigens CEA, CA 15-3 and CA 125 were determined in serous effusions (EF) from patients (pts) with breast cancer. As controls, serous effusions from patients with benign and other malignant diseases were used. The EF levels were also compared with those of serum. CA 15-3 was elevated (greater than 35 U/ml) in 65.7% of breast cancer EF, in 39.3% of EF in various other malignant diseases and in 0% of benign EF. CEA was elevated (greater than 9 ng/ml) in 37.5% of breast cancer EF, in 17.9% of EF of various other malignant diseases and in 27% of benign EF. CA 125 was elevated (greater than 35 U/ml) in 93.8% of breast cancer EF, in 78.6% of EF of various other malignant diseases and in 58.8% of benign EF. There was a statistically significant correlation between EF and serum values for the markers studied. Sensitivity and specificity for CA 15-3 were 65.7% and 76.6%, for CEA 37.5% and 77.7% and for CA 125 93.8% and 28.7%, respectively. CA 15-3 is a marker with definite diagnostic accuracy compared to CEA and CA 125 in breast cancer EF. CA 125 appears to derive from proliferating mesothelia rather than cancer cells alone and occurs in a broad spectrum of malignant as well as benign EF. The above markers should not be used alone for diagnosis of breast cancer in patients with serous effusions.     

Serous ovarian cyst fluids contain high levels of endometrial placental protein 14.

This paper reports the detection and characterization of endometrial placental protein 14 (PP14) in human ovarian cyst fluids. PP14 from ovarian cyst fluid has the same molecular size as PP14 purified from human amniotic fluid. No clear difference was found in the PP14 concentrations between benign, borderline and malignant cyst fluids, but serous ovarian cyst fluids had significantly higher PP14 concentrations (median 253.3 micrograms/l) than mucinous cyst fluids (median 17.5 micrograms/l).     

Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status

CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.     

A comparison of the growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian tumours

The growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian malignancy, benign ovarian tumours and non-tumour related gynaecological conditions have been investigated using an ovarian carcinoma cell line (OAW 42), mesothelial cells (58MC) and rat kidney cells (NRK-49F). Colony stimulating activity (CSA) for tumour cells and transforming activity (TA) for mesothelial cells were weakly correlated, but whereas elevated TA was tumour-associated, CSA was not. However, TA was not cancer-associated and, although the difference between the mean TA values of benign and malignant cyst fluids was of borderline significance, some benign cyst fluids from cystadenomas showed high TA values. Higher levels of TA in the cystadenomas showed a significant correlation with the menopausal status of the patient and higher levels of TA in the malignant cyst fluid/peritoneal fluid groups were associated with more advanced disease. Results indicated that some fluids contained TGF-beta-like activity, but there was no direct evidence for the presence of TGF-alpha/EGF-like activity in the fluids. Heparin inhibited clonogenic growth of tumour cells but not mesothelial cells. The reduced CSA which was observed after treatment of fluids with both heparin and thrombin implicated coagulation factors in the manifestation of CSA. It was concluded that CSA in the fluids was due, at least partly, to fibrin coagulation, and TA was due to unknown growth factor(s) which may include TGF-beta-like activity. The results are discussed in the context of the aetiology of ovarian carcinoma, and the possible clinical significance of TA.     

HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases

The aim of this study is to evaluate a new tumour marker, HE4, in comparison with CA 125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in healthy women and in patients with benign and malignant gynaecological diseases. CA 125 and HE4 serum levels were determined in 66 healthy women, 285 patients with benign gynaecological diseases (68 endometriosis, 56 myomas, 137 ovarian cysts and 24 with other diseases), 33 patients with non-active gynaecological cancer and 143 with active gynaecological cancer (111 ovarian cancers). CA 125 and HE4 cut-offs were 35 U/mL and 150 pmol/L, respectively. ROMA algorithm cut-off was 13.1 and 27.7 for premenopausal or postmenopausal women, respectively. HE4, CA 125 and ROMA results were abnormal in 1.5%, 13.6% and 25.8% of healthy women and in 1.1%, 30.2% and 12.3% of patients with benign diseases, respectively. Among patients with cancer, HE4 (in contrast to CA 125) had significantly higher concentrations in ovarian cancer than in other malignancies (p < 0.001). Tumour marker sensitivity in ovarian cancer was 79.3% for HE4, 82.9% for CA 125 and 90.1% for ROMA. Both tumour markers, HE4 and CA 125 were related to tumour stage and histological type, with the lowest concentrations in mucinous tumours. A significantly higher area under the ROC curve was obtained with ROMA and HE4 than with CA 125 in the differential diagnosis of benign gynaecological diseases versus malignant ovarian cancer (0.952, 0.936 and 0.853, respectively). Data from our population indicate that ROMA algorithm might be further improved if it is used only in patients with normal HE4 and abnormal CA 125 serum levels (cancer risk for this profile is 44.4%). ROMA algorithm in HE4 positive had a similar sensitivity and only increases the specificity by 3.2% compared to HE4 alone.     

Immunoradiometric assay of CA 125 in effusions. Comparison with carcinoembryonic antigen

The levels of CA 125 antigen were measured in 167 effusions from 150 patients using radioimmunoassay, and the results compared with the levels of carcinoembryonic antigen (CEA) in the fluids. This study was carried out to test a hypothesis that measuring the combined levels of selected tumor associated antigens in effusions could predict the primary source of malignancy. The results indicate that an elevated fluid CA 125 level (greater than 14,000 U/ml-68,000 U/ml) and a negative fluid CEA level (less than 5 ng/ml) is suggestive of serous and endometrioid carcinoma of ovary, and adenocarcinoma of the endometrium and fallopian tube. Alternatively, an elevated fluid CEA level (14 ng/ml-600 ng/ml) and a negative CA 125 level (20-5000 U/ml) is seen in metastatic carcinomas of breast, lung, gastrointestinal tract, and mucinous cystadenocarcinoma. Lymphomas, melanomas, and benign effusions are negative for both antigens. The combined use of CEA and CA 125 antigen in fluids is useful in the differential diagnosis of adenocarcinoma of unknown primary.     

Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions.

We evaluated the diagnostic utility of simultaneous determination of 5 tumor markers, CEA, CA 125, CA 15-3, CA 19-9 and cytokeratin 19 (CYFRA 21-1), in fluid and serum from 101 patients, 52 with pleural effusion (22 malignant) and 49 patients with ascites (14 malignant). Tumor marker concentrations in fluid from patients with malignant effusions were significantly higher than those obtained in benign fluids or serum. However, there are two types of tumor markers: those released/secreted by normal mesothelia such as CA 125 and cytokeratin 19 (higher levels in benign fluids than in serum) and non-released/secreted tumor markers (low concentrations in benign fluids) such as CEA, CA 19-9 and CA 15-3. The fluid/serum (F/S) ratio showed better sensitivity with maximum specificity than a single determination in fluid for CEA, CA 15-3 and CA 19-9, but not for CA 125 and CYFRA. The combination of a F/S ratio greater than 1.2 and a cut-off of 5 ng/ml for CEA, 30 U/ml for CA 15-3 and 37 U/ml for CA 19-9 showed sensitivities of 58, 57 and 44%, respectively, and a specificity of 100%, with a combined sensitivity of 82% for overall effusions and 79% for fluids with negative cytology with a specificity of 100%. In conclusion, the use of the F/S ratio in nonsecreted tumor markers such as CEA, CA 19-9 and CA 15-3 improve the sensitivity and specificity and allow standardization of the cut-off.     

Placental protein 5 in benign and malignant ovarian cyst fluids

Placental protein 5 (PP5), a serine protease inhibitor, was measured by radioimmunoassay in fluids aspirated from benign and malignant cystic ovarian tumours. PP5 was found in 7 out of 9 malignant and in 12 out of 29 benign cyst fluids (p less than 0.01), the levels ranging from 3.0 to 73.4 micrograms/l. No PP5 was found in the corresponding serum samples from 4 patients whose malignant cystadenocarcinomas contained PP5. In those tumours where PP5 was found, no difference was observed in the PP5 levels between benign and malignant, or between serous and mucinous tumours.     

Tumour-associated trypsin inhibitor (TATI): comparison with CA125 as a preoperative prognostic indicator in advanced ovarian cancer.

We have evaluated the prognostic value of tumour-associated trypsin inhibitor (TATI) in stage III or IV ovarian cancer. Tumour-associated trypsin inhibitor (TATI) and CA 125 were determined in serum samples from 66 patients taken before primary surgery. TATI was elevated (> 22 micrograms l-1) in 27 patients (41%). These had a 5 year cumulative survival of 8%, whereas survival was 45% in 39 patients with normal preoperative TATI values. By contrast, the preoperative CA 125 level did not predict survival. In multivariate analysis which included age, stage, histological grade and preoperative TATI and CA 125 levels, patients with elevated preoperative TATI levels had a 2.3-fold relative risk of death (95% confidence interval 1.23-4.20; P = 0.002) compared with patients with normal preoperative levels. This result was comparable with the predictive value of primary residual tumour size, since patients with residual tumour larger than 2 cm in diameter had a 5.2-fold relative risk of death (95% confidence interval 2.55-10.68) compared with patients with a smaller or no residual tumour. Thus, preoperative determination of serum TATI may have a place in the pretreatment evaluation of patients with advanced ovarian cancer.     

Increased insulin-like growth factor binding protein-2 (IGFBP-2) gene expression and protein production lead to high IGFBP-2 content in malignant ovarian cyst fluid.

Expression of insulin-like growth factor-I (IGF-I), its receptor and IGF-binding proteins (IGFBPs) by ovarian cancer cells and its mitogenic effect on these cells in vitro, suggest that IGF-I may have a role in regulation of human ovarian cancer. We have recently shown IGFBP-2 to be markedly elevated in malignant ovarian cyst fluid in vivo. To identify the origin of increased IGFBP-2 in these cyst fluids, the gene expression and protein content of IGFBP-2 were investigated in 14 malignant and four benign epithelial ovarian neoplasms. IGFBP-2 mRNA was detected in all ovarian specimens and was 2- to 30-fold higher in malignant than in benign neoplasms. Within the malignant tissues IGFBP-2 mRNA levels correlated with the aggressiveness of the tumour and were higher in invasive tumours than in those with borderline pathology. Southern blot analysis revealed no amplification of IGFBP-2 gene in the DNA samples from ovarian tumours regardless of their nature. IGFBP-2 was the major binding protein in tissue extracts, as measured by both Western ligand blotting and immunoblotting, and was significantly higher in malignant than in benign neoplasms. These findings were further supported by immunohistochemical detection of IGFBP-2 in tumour sections. Our data suggest that increased local production by the tumour in vivo is responsible for the increased IGFBP-2 levels in the cyst fluid bathing the ovarian malignancy. This may represent an autocrine regulatory mechanism for IGF-I proliferative effect of ovarian cancer.     

Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours

BACKGROUND: We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours. MATERIALS AND METHODS: Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous). RESULTS: A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours. CONCLUSION: Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours.     

Values of carcinoembryonic antigen, elastase 1, and carbohydrate antigen determinant in aspirated pancreatic cystic fluid in the diagnosis of cysts of the pancreas

The levels of carcinoembryonic antigen (CEA), elastase 1, and carbohydrate antigen determinant (CA 19-9) in the pancreatic cystic fluid and the serum from five patients with cystadenocarcinoma of the pancreas, one patient with retention cyst due to pancreatic carcinoma, three patients with cystadenoma, and eight patients with benign pseudocyst accompanying or following pancreatitis, were determined by immunoassay technique. Fluid from pancreatic cysts was obtained by ultrasonically-guided percutaneous fine-needle aspiration biopsy. The specimens were centrifuged and the supernatant was used for the measurement of CEA, elastase 1, and CA 19-9, while the cell pellet was examined cytologically. The levels of CEA in the aspirated fluid were significantly higher in patients with malignant cysts of the pancreas than in those with benign cystadenomas and pseudocysts. In contrast, the levels of elastase 1 were significantly lower in patients with malignant cysts than in those with benign pancreatic cysts. Although the levels of CA 19-9 were significantly higher in patients with malignant cysts than in those with pseudocysts, the overlap between the values of patients with malignant and benign pancreatic cysts is too great. The serum CA 19-9 was most useful, however, to distinguish an individual patient with malignant cysts of the pancreas from those with benign pancreatic cyst, since there were no significant differences between the levels of serum CEA and elastase 1 in patients with malignant and benign pancreatic cysts. Correct diagnoses were made cytologically in 4 (66.7%) of 6 patients with malignant cysts. In two patients with malignant cyst, in whom no cancer cells were detectable in the aspirated materials, levels of CEA were abnormally high, but high levels of elastase 1 did not occur. Therefore, the combined measurement of CEA and elastase 1 in the aspirated cystic fluid of the pancreas could be used as an aid in diagnosis of malignant cysts of the pancreas.     

MDM2 Expression in Serous and Mucinous Epithelial Tumours of the Ovary

Background: Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute2(MDM2) cell cycle regulator is a protooncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant). Materials and Methods: This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal antiMDM2 antibody for immunohistochemistry. Results: MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chisquare test 0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test 0.04). Conclusions: Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.