Appendiceal carcinoma metastatic to the ovaries and mimicking primary ovarian tumors

Primary appendiceal carcinomas are a rare source of metastases to the ovaries. Three cases are reported here, and 25 others are reviewed from the English literature. The recognition of this entity is important, since the metastases may mimic an ovarian primary tumor clinically, and because of the propensity for a recognized appendiceal carcinoma to relapse in the ovaries. Therapeutic implications dictate that the appendix should always be carefully examined during exploration for ovarian masses, and prophylactic appendectomy should be considered, as part of the treatment of ovarian carcinomas.     

Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary.

Metastatic pancreatic mucinous adenocarcinomas in the ovaries can be difficult to distinguish from primary ovarian mucinous neoplasms because the former can simulate the latter grossly and histologically and both tumor types share the same cytokeratin 7/cytokeratin 20 immunoprofile. We previously reported the utility of loss of Dpc4 expression in distinguishing metastatic pancreatic carcinomas from primary ovarian mucinous tumors. Recently several new pancreatic carcinoma markers have been identified, including mesothelin, fascin, and prostate stem cell antigen (PSCA). In this study we investigate the expression patterns of these markers in 35 primary ovarian mucinous tumors (28 atypical proliferative [borderline] tumors and 7 invasive carcinomas) and 11 metastatic pancreatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors expressed mesothelin (17%), fascin (26%), and PSCA (43%) less frequently than metastatic pancreatic adenocarcinomas (73%, 73%, and 82%, respectively). Expression of all three markers was seen only in metastatic pancreatic adenocarcinomas (45%), and coexpression of at least two markers was observed significantly more frequently in metastatic (82%) than primary ovarian mucinous tumors (17%). Our results indicate that an immunohistochemical panel including Dpc4, mesothelin, fascin, and PSCA is useful for evaluating difficult mucinous tumors in the ovary when the differential diagnosis includes metastatic pancreatic adenocarcinoma.     

Carcinoembryonic antigen (CEA) and carbohydrate determinant 19-9 (CA 19-9) localization in 121 primary and metastatic ovarian tumors: an immunohistochemical study with the use of monoclonal antibodies

An immunoperoxidase study, using the Avidin-Biotin-Peroxidase complex method and the monoclonal antibodies, anti-carcinoembryonic antigen (CEA) and anti-carbohydrate determinant 19-9 (CA 19-9), was carried out on 108 common epithelial tumors of the ovary and 13 epithelial tumors metastatic to the ovary. Primary mucinous tumors were positive in 62% of the cases (benign, 15%; borderline, 80%; and carcinomatous, 100%) with anti-CEA. None of the serous tumors were positive with anti-CEA, but 27% (benign, 23%; borderline, 40%; and carcinomatous, 20%) were positive with anti-CA 19-9. With anti-CEA, 30% of the endometrioid carcinomas, 50% of the malignant mesodermal mixed tumors, 14% of the clear cell carcinomas, 36% of the Brenner tumors, and 83% of the metastatic carcinomas from the large intestine were positive. With anti-CA 19-9, 76% of the mucinous, 40% of the endometrioid, 25% of the malignant mesodermal mixed tumors, 57% of the clear cell carcinomas, 45% of the Brenner tumors, and all the metastatic carcinomas from the large intestine were positive. All the undifferentiated carcinomas were unreactive with both antibodies. Although neither CEA nor CA 19-9 is a specific marker for any type of ovarian tumor or for malignancy per se, the presence of the former antigen can be useful in differentiating serous from mucinous tumors. Moreover, demonstration of either antigen in a variety of tumors may indicate its potential value as a serum marker in monitoring the course of the patient.     

Carcinoembryonic antigen in patients with residual ovarian cancer: Clinical and pathological correlations

The level of Carcinoembryonic antigen (CEA) in serum was estimated before the commencement of chemotherapy and/or radiotherapy in 130 patients with residual ovarian cancer. CEA was detected in 64% of the patients. The associated clinical and pathological features were examined. No differences were found in the distribution of patients who were CEA positive and CEA negative in relation to the features studied. However, a correlation between serum CEA levels on one hand and site of tumor, organ involved, and estimated tumor volume on the other was found among the CEA-positive patients. No direct correlation was observed between CEA levels and subsequent behavior of the disease, except for patients who showed CEA levels exceeding 20 ng/ml. In these patients, the risk of progressive disease increased from 40 to 63% after 12 months of follow-up.     

Biomarker conservation in primary and metastatic epithelial ovarian cancer

PURPOSE: The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers. METHODS: Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied. RESULTS: A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse. CONCLUSIONS: With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.     

Accuracy of frozen section in distinguishing primary ovarian neoplasia from tumors metastatic to the ovary.

Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors. The diagnosis of malignancy is usually straightforward but in some cases it may be difficult to distinguish whether tumors are of ovarian origin or represent matastases from other sites. Recently, Seidman and colleagues presented a simple algorithm based on tumor size and unilateral versus bilateral involvement to aid in intra-operative assessment of ovarian mucinous neoplasms. In this study we have reviewed the accuracy of frozen section in distinguishing primary ovarian malignancies from tumors metastatic to the ovaries encountered in two hospitals over a 5-year period. The algorithm was also applied to our cases retrospectively irrespective of histological type. Nine hundred fourteen ovarian frozen sections were performed in the study period including 266 cases with a final diagnosis of malignancy. Thirty-seven malignancies (13.9%) were of metastatic origin (exclusing one lymphoma), 21 of which (58.8%) were correctly identified on frozen section. In 5 additional cases metastatic origin was included in the differential diagnosis while a primary ovarian tumor was favored un 11 cases (29.7%). Application of the algorithm to the metastatic tumors led to correct classification in 26/33 (78.8%) assessable cases. Conversely, 195/228 primary ovarian malignancies were correctly identified intra-operatively but the possibility of extra-ovarian malignancy was considered or not excluded in 33 cases (14.5%). Application of the algorithm to the latter problematic primary ovarian tumors overall was not helpful in distinguishing primary or metastatic origin. However if only low-grade primary adenocarcinomas were considered then 10/12 assessable cases were correctly assigned. In conclusion frozen section is only moderately successful in distinguishing primary ovarian malignancies fron tumors metastatic to the ovaries. The simple algorithm proposed by Seidman and colleagues for assessment of ovarian mucinous tumors is helpful and can be applied to low-grade adenocarcinomas of other histological types.     

Steroid receptors and ovarian tumors: variation within primary tumors and between primary tumors and metastases

Estrogen and progesterone receptors have been measured in primary and secondary ovarian carcinoma in eight patients, in bilateral ovarian tumors in 16 patients, and from multiple sites within the same tumor in 16 patients (12 primary and 4 secondary). In the majority of cases, metastatic tumors contained less receptors than their primary tumors. Marked variations in receptor content were noted within the same tumor and between bilateral tumors. This variation in receptor levels may explain the discrepancy between the presence of receptors and the response to hormonal treatment. Multiple sites of ovarian carcinoma need to be assayed for receptor content before a final decision can be made on receptor status.     

Preoperative clinical and radiological features of metastatic ovarian tumors

Purpose

To investigate the clinical characteristics and pre-operative imaging features of non-genital metastatic ovarian tumors.

Methods

A retrospective case series study that compared 18 patients with histologically confirmed non-genital metastatic ovarian tumors (the study group) with 25 patients who were diagnosed with a primary ovarian cancer (control group).

Results

The most common primary disease was breast cancer (n = 10; 55 %), followed by colon cancer, gastric cancer, lymphoma, and unknown primary malignancy. The diagnosis of the previous primary neoplasm preceded the ovarian tumor diagnosis by 1–20 years (mean 7 years). No differences were found in the presenting signs and symptoms between the two groups. Statistically significant differences were noted between the two groups in the composition of the adnexal mass on sonography (p < 0.0005) and the CA-125 levels (p = 0.007). The presence of a complex adnexal mass with papillary projections and CA-125 >170 U/ml predicted primary ovarian cancer in 95.7 % of patients. Pre-operative CT scan revealed a greater tendency toward omental involvement and ascites in the control group (p = 0.058). The median risk of malignancy index (RMI) 2 score was significantly higher in the control group compared to the study group (8,000 and 1,120 respectively, p = 0.001). Using a RMI 2 cut-off level of 3,800 for diagnosing primary ovarian cancer versus metastatic ovarian cancer, the sensitivity was 70 %, with a positive predictive value of 87.5 %.

Conclusion

Pre-operative sonography findings, CA-125 levels and RMI 2 scores can be highly accurate in differentiating between primary and metastatic ovarian tumors.     

Somatic mitochondrial DNA mutations in primary and metastatic ovarian cancer

OBJECTIVE: To date, most mtDNA mutations in cancer have been identified in the control region (D-loop) containing the major promoters. However, almost all studies used one sample per tumor and there is no clear evidence whether metastatic deposits harbor different mtDNA variants. To establish whether different mtDNA variants can be found in the same cancer but at different sites, we analyzed a series of unilateral and bilateral primary epithelial ovarian cancers as well as paired metastatic tumor deposits. METHODS: We sequenced the D-loop region in 52 different tumor samples of 35 ovarian cancer cases, as well as matched normal tissues. Seventeen of those 35 cases had bilateral ovarian cancer, with a sample from each tumor analyzed. RESULTS: Eighty-six polymorphisms (4 new in ovarian cancer) were detected, and 9 different somatic mtDNA mutations were found in 26% (9 of 35) of ovarian cancer cases; all were homoplasmic in nature. Six of the mutations were novel in ovarian cancer. In 24% (4 of 17) of cases with bilateral ovarian tumors, different mtDNA variants were found between paired tumors, suggesting the presence of different clonal populations of cancer cells. Metastatic tumor deposits showed identical mtDNA variants to those found in at least one of the ovarian tumors in cases with bilateral ovarian cancer. CONCLUSION: Our data demonstrate that multiple tumor samples from the same patient may harbor different mtDNA variants.     

Carcinoembryonic antigen in high risk pregnancies

The significance of carcinoembryonic antigen (CEA) measurement was evaluated in 25 pregnant women with diabetes mellitus, 15 Rh negative sensitized and nine prolonged pregnancies. Another 114 women with normal pregnancy served as controls. Values in maternal and umbilical cord serum and in amniotic fluid did not change appreciably through 24-42 weeks' gestation. No significant difference in maternal serum, cord serum and amniotic fluid CEA values was found between diabetic, Rh negative sensitized and normal pregnancies at the corresponding weeks. Similar findings were obtained in prolonged pregnancies, except the values in amniotic fluid which were significantly higher than in normal pregnancies due to the presence of meconium. These results suggest that the measurement of CEA in high risk pregnancies is not useful in predicting fetal condition.     

Proliferative activity in primary ovarian carcinoid tumors.

The proliferative potential of six primary ovarian carcinoids with different clinical outcome and histogenetic origin was examined immunohistochemically. The results showed that two cases with extremely high level of proliferative activity were associated with metastatic spread. In the remaining tumors, the examined factor was found to be at low level comparable with excellent prognosis of typical carcinoids in other locations. The preliminary results showed a possibility of a prognosis prediction according to typing of the ovarian carcinoids into two categories, i.e., tumors of low and intermediate malignancy. Topoisomerase II-alpha and Ki-67 are suitable markers giving valuable information about this phenomenon.     

Second primary cancers following borderline ovarian tumors

Background  

Several studies have reported an increased risk of second primary cancers subsequent to invasive epithelial ovarian cancer. However, there is no adequate data regarding such risk in borderline ovarian tumors (BOTs). The aim of this study was to evaluate the risk of subsequent second primary cancers among women with BOTs.     

Carcinoembryonic antigen activity in human seminal plasma

Carcinoembryonic antigen (CEA) immunoreactivity in the seminal plasma of 101 men was studied by enzyme immunoassay (EIA). It was found that (1) mean CEA (or CEA-like activity) in seminal plasma is about 8.5 times higher than the upper CEA limit in normal serum; (2) there is no statistically significant difference between the antigen levels of normal controls and various groups of men with fertility problems, as well as between men with normal and those with abnormal spermiogram; (3) the prostate seems to be the main site of origin of CEA or CEA-like activity in the seminal plasma.     

Quantitative protein changes in metastatic versus primary epithelial ovarian carcinoma

Primary and metastatic ovarian carcinomas from six patients were obtained during primary exploratory laparotomy. Tumor cells were synthetically radiolabeled with [35S]methionine. Radiolabeled cellular proteins of the primary and metastatic cells were examined by two-dimensional polyacrylamide gel electrophoresis followed by autoradiography. Computer assisted analysis of the resultant autoradiograms revealed that the amounts of only two proteins, p35 and p36, were consistently and significantly decreased in the metastatic tumor cells. No other consistent differences in protein synthesis between primary and metastatic tumors were detected.     

Histologic subtypes and laterality of primary epithelial ovarian tumors

OBJECTIVES: To determine if the likelihood of bilateral primary ovarian tumors differs by histologic subtype. METHODS: Using data collected by the Surveillance Epidemiology and End Results (SEER) program, the analysis included 22,328 women 25-84 years of age who were diagnosed with a borderline or malignant epithelial ovarian tumor during 1992-2000, categorized as to laterality and histologic subtype. RESULTS: Malignant serous tumors were bilateral in 57.5% of cases. Corresponding figures for mucinous, clear cell, endometrioid and other epithelial tumors were 21.3%, 13.3%, 26.8%, and 35.6%, respectively. Borderline serous tumors were bilateral in 29.8% of the cases compared to only 7.0% of mucinous tumors. The tendency for serous tumors to present as bilateral was consistent across all categories of race, age, and stage. CONCLUSIONS: Serous tumors of the ovary are more commonly bilateral than ovarian tumors of other histologic subtypes. The reasons for this tendency remain to be determined.     

Hepatocyte paraffin 1 antibody does not distinguish primary ovarian tumors with hepatoid differentiation from metastatic hepatocellular carcinoma.

Anti-hepatocyte antibody, hepatocyte paraffin 1, is a monoclonal antibody that is highly specific for normal and neoplastic hepatocytes and that can differentiate hepatocytic from nonhepatocytic tumors. This marker has been rarely studied in extra-hepatic tumors and to our knowledge has not been investigated in ovarian tumors with hepatoid differentiation. We studied hepatocyte paraffin 1 immunoreactivity in a series of ovarian hepatoid carcinomas, ovarian hepatoid yolk sac tumors (YSTs), and hepatocellular carcinomas metastatic to the ovary to assess the potential utility of hepatocyte paraffin 1 in differential diagnosis. Hepatocyte paraffin 1 positivity was seen in three of seven ovarian hepatoid carcinomas, five of eight hepatoid yolk sac tumors, and six of eight metastatic hepatocellular carcinomas. The extent of positivity ranged from <25% to >50% of the tumor cells. There was strong coarsely granular cytoplasmic staining in all three tumor types without a distinctive staining pattern in any group. The degree of hepatic differentiation correlated with hepatocyte paraffin 1 positivity in the three groups: 83% of the well differentiated tumors, 50% of the moderately differentiated tumors, and none of the poorly differentiated tumors were positive. All ovarian hepatoid carcinomas were either immunoreactive for alpha-fetoprotein or had an elevated serum alpha-fetoprotein level; more than half of these tumors were hepatocyte paraffin 1 negative. All but one hepatocyte paraffin 1 negative hepatoid yolk sac tumor and ovarian hepatocellular carcinoma were also negative for alpha-fetoprotein. In conclusion, hepatocyte paraffin 1 is positive in primary ovarian tumors with hepatoid differentiation, with the degree of hepatocyte paraffin 1 positivity correlating with the degree of hepatoid differentiation. Hepatocyte paraffin 1, however, is not useful in distinguishing metastatic hepatocellular carcinoma from primary ovarian hepatoid carcinoma or hepatoid yolk sac tumor.     

Carcinoembryonic antigen in genital infections caused by HPV

The immunohistochemical search for the carcino-embryonic antigen (CEA) was positive in 28.14 per cent of the cases of plane cervical condylomata, in 25 per cent of the cases of infections of the vulva by HPV, and in up to 40 per cent of the cases of cervical or vulvar lesions. These data are in accordance with those reported in the literature, even if the number of cases studied is too limited to enable us to make a significant comparison. As a result, the CEA might prove to be a useful marker for a more accurate biological and chemical classification of genital lesions by HPV.     

Carcinoembryonic antigen and related molecules in normal and transformed trophoblast

Carcinoembryonic antigen (CEA, CD66e) and CEA-related cell adhesion molecules (CEACAMs) are important mediators in remodeling of diverse human tissues, and modulators of cell proliferation and differentiation. Expression by normal and transformed trophoblast of gestational trophoblastic diseases (GTDs), isolated cytotrophoblast and choriocarcinoma cell lines is presented here. Immunocyto/histochemistry of normal placenta (n=9), invasive mole (n=8), choriocarcinoma (n=7), a placental site trophoblastic tumor, cytotrophoblast in primary culture and JAr and JEG-3 cells was performed using polyclonal anti-CEA and specific monoclonal anti-CEA antibodies. Data were analyzed and scored using Mann-Whitney Test. CEA and CEA-related molecules were identified by Western blot and immunoaffinity chromatography in JAr and JEG-3 cells and extracts of 1st and 3rd trimester of pregnancy tissue and cytotrophoblast cell lysates. CEA is expressed throughout pregnancy, in first trimester predominantly in syncytiotrophoblast, but also in villous cytotrophoblast and extravillous trophoblast. Data presented here demonstrate that CEA is significantly increased in transformed trophoblast of GTDs (p<0.05). Both cytotrophoblast in primary culture and choriocarcinoma cell lines express CEA, with staining of granular deposits in JAr and cell membrane in JEG-3. The results suggest that CEA (CD66e) and other CEA-related protein(s) could be involved in trophoblast differentiation.