A pilot study of ovarian cancer chemoprevention using medroxyprogesterone acetate in an avian model of spontaneous ovarian carcinogenesis

OBJECTIVE: Our previous studies have documented the feasibility of using the laying hen, Gallus domesticus, as a model of spontaneous ovarian carcinogenesis. This study was performed to determine the ability of medroxyprogesterone acetate (Depo-Provera) to reduce the frequency of spontaneously developing reproductive tract adenocarcinoma in the avian model. METHOD: Four hundred 3-year-old hens were in a two-arm trial designed to determine the frequency of epithelial reproductive tract adenocarcinomas. Animals were designated to receive three injections of 100 mg Depo-Provera versus no injection over a 16-month period. Both groups were subjected to two induced molts 12 months apart. Egg counts were obtained and decreased egg production was documented in the treated hens due to Depo-Provera. At the end of 16 months surviving animals were sacrificed and the frequency of reproductive tract adenocarcinoma was determined histologicically. RESULTS: Histologic information was obtained from the 293 hens that completed the full prescribed course of study. At the time of necropsy, multiple hens had evidence of carcinomatosis and massive ascites consistent with metastatic reproductive tract adenocarcinomas. Of the tissues examined from the informative cases gathered at the time of sacrifice, there was evidence of a reduction of reproductive tract adenocarcinoma observed in the Depo-Provera group (45/127-35%) when compared to the control group (69/166-42%). A risk reduction of 15% is observed in the treatment group (risk ratio 0.85: 95% confidence interval 0.63-1.15). CONCLUSION: The high rate of reproductive tract adenocarcinoma observed in this study supports the avian hen as a valid model of spontaneous ovarian carcinogenesis in which to test chemoprevention strategies and provides a unique opportunity for investigating the pathogenesis of ovarian carcinoma. The current histologic findings are consistent with the theory that a reduction of ovulatory events may prevent the development of ovarian adenocarcinoma.     

Ovarian tumor expression of an oviductal protein in the hen: a model for human serous ovarian adenocarcinoma

OBJECTIVE: We hypothesized that ovarian tumors without oviductal involvement would not express the oviductal protein ovalbumin, the major protein found in the magnum of the hen's oviduct. METHODS: On the basis of gross visual examination, tissues samples were removed from hens determined to have ovarian tumors and were processed, embedded in paraffin, sectioned, mounted on glass slides, and stained with hematoxylin and eosin. Ovarian tumors and other peritoneal lesions were evaluated histologically. Paraffin sections of ovarian and oviductal tissue were deparaffinized and evaluated for the protein expression of ovalbumin, proliferating cell nuclear antigen (PCNA), and progesterone receptor (PR). RESULTS: Hens with ovarian adenocarcinoma without (n = 10) or with (n = 6) oviductal involvement were positive for ovalbumin in the ovary. Ovary sections from normal hens (n = 9) were negative, and oviductal sections from normal hens (n = 3) were positive for ovalbumin. Expression of PCNA protein was abundant in all ovarian tumors (16 of 16). Oviductal epithelial cells strongly expressed PCNA protein. Expression of PR was observed in 9 of 14 ovarian tumors. CONCLUSION: The presence of ovalbumin in ovarian tumors in the absence of any oviductal involvement suggests that ovarian tumors dedifferentiate during the disease process and thereby resemble serous-type ovarian tumors in women.     

人胎儿卵巢组织转化生长因子～α与表皮生长因子受体的表达

目的 探讨转化生长因子－α（ＴＧＦ－α）和表皮生长因子受体（ＥＧＦＲ）在人胎儿卵巢的表达与定位及培养前后的变化。方法 收集２０份胎龄为１６－４０周因各种原因死亡的女性胎儿卵巢标本,对其中１０份卵巢标本分３,６,９ｄ进行组织培养,采用免疫组织化学方法测定ＴＧＦ－α和ＥＧＦＲ蛋白在人胎儿卵巢组织中的表达。结果 ＴＧＦ－α在１７份胎儿卵巢卵母细胞,７份卵泡细胞及１３份基质细胞有性表达,ＥＧＦＲ在１９份卵     

The cytokeratin profiles of ovarian common "epithelial" tumors

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.     

Jejunal adenocarcinoma presenting as a primary ovarian carcinoma

OBJECTIVE: The aim of this case report was to evaluate the impact of immunohistochemical markers in diagnosing the primary site of adenocarcinoma in the abdominopelvic region. METHODS: Surgicopathologic data were obtained from laparotomy and necropsy. Paraffin-embedded tissue from the ovary and jejunum was stained with hematoxylin and eosin, as well as with immunohistochemical stains for cytokeratin 20 and cytokeratin 7. RESULTS: A 53-year-old African American woman underwent an emergency laparotomy due to small bowel obstruction. During the operation, in addition to a complex adnexal mass as the cause of obstruction, a small solid jejunal tumor was also identified. Pathologic evaluation of the two sites demonstrated an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 and revealed negative staining for cytokeratin 7. These results confirmed the diagnosis of intestinal primary with ovarian metastasis, which was initially misdiagnosed as an ovarian primary. CONCLUSION: Given the potential difficulty in determining the primary site of these tumors, immunohistochemistry proved to be a useful tool in reaching the correct diagnosis.     

Immunohistochemical and immunoelectron microscopic study of an amylase-producing, CA19-9 positive ovarian mucinous cystadenocarcinoma

A 75-year-old woman with a right ovarian tumor revealed high levels of serum amylase and CA19-9 which decreased to within normal limits after the operation. A histopathological study of surgically excised tumor tissue revealed a mucinous cystadenocarcinoma. The tumor was composed of three elements: adenoma, adenoma with low potential malignancy, and adenocarcinoma. Using the light microscopic indirect immunoperoxidase technique for amylase and CEA, and the Avidin-Biotin affinity technique for CA19-9 and CA12-5, the amylase and CA19-9 were stained in the cytoplasm of the adenoma and adenocarcinoma although CEA was stained only in the cytoplasm of the adenocarcinoma. An ultrastructural study using the immunoperoxidase method revealed that CA19-9 was positive in the apical portion of the tumor cells and amylase was positive in the entire secretory vesicles of the tumor cells. Furthermore, ciliated tumor cells derived from fallopian tube epithelium were not observed in the light and electron microscopic specimens.     

Expression of transforming growth factor-alpha, epidermal growth factor, and epidermal growth factor receptor in follicles of human ovarian tissue before and after cryopreservation

OBJECTIVE: To study the expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and EGF receptor in follicles of human ovarian tissue. DESIGN: A retrospective, controlled comparative study. SETTING: In vitro fertilization laboratory of a university hospital. PATIENT(S): Fifteen women with regular menstrual cycles who underwent laparoscopy and the biopsy of ovarian tissue. INTERVENTION(S): Paraffin sections were prepared from ovarian tissues, followed by immunohistochemical staining of TGF-alpha, EGF, and EGF receptor. MAIN OUTCOME MEASURE(S): Immunostaining for TGF-alpha, EGF, and EGF receptor in follicles of fresh and frozen ovarian tissues. RESULT(S): Immunoreactivities for TGF-alpha and EGF receptor were observed simultaneously in the oocytes of primordial, primary, preantral, and antral follicles. Strong staining for TGF-alpha and EGF receptor was present in thecal cells. The TGF-alpha and EGF receptor was also expressed in some granulosa cells of primary to antral follicles. The EGF only stained weakly in the oocytes of primordial and primary follicles and in thecal cells. There was no difference in staining patterns for TGF-alpha, EGF, and EGF receptor between fresh and frozen ovarian tissues. CONCLUSION(S): The TGF-alpha and EGF receptor was expressed in primordial to antral follicles, indicating a role of TGF-alpha in regulating follicular development through binding to the EGF receptor. Freeze-thawing did not substantially alter immunoreactivites for TGF-alpha, EGF, and EGF receptor in frozen ovarian tissue.     

卵巢上皮性癌患者外周血中癌细胞的检测

目的 检测卵巢上皮性癌患者外周血干细胞（ＰＢＳＣ）中有无癌细胞污染及原发晚期卵巢上皮性细胞患者外周循环血中有无癌细胞。方法 应用卵白素－生物素酶－复合物（ＡＢＣ）法,检测２例患者ＰＢＳＣ及８例患者外周血。为了确定ＡＢＣ法检测血中癌细胞的灵敏度,分别用卵巢癌细胞系ＳＫＯＶ３,３ＡＯ以及从浆性乳头状腺癌,未分化腺癌虱腹水中得到的原代癌细胞,制成癌细胞与单核细胞的不同浓度模型,应用单克隆抗体ＣＯＣ１８３     

表皮生长因子受体在卵巢浆液性肿瘤中表达的研究

目的：研究表皮生长因子受体在卵巢浆液性肿瘤中的表达，并探讨其表达与肿瘤的性质、临床分期及组织学分级的关系。方法：用免疫组化ＡＢＣ法。结果：表皮生长因子受体在卵巢浆液性腺癌和浆液性交界性瘤中的表达差异无显著性，但均显著高于其在腺瘤中的表达。表皮生长因子受体的表达与卵巢浆液性腺癌的临床分期无关，在低分化腺癌中的表达显著高于中分化腺癌。结论：表皮生长因子受体在卵巢浆液性腺癌的发生发展过程中起着重要作用，可作为判断肿瘤恶性度的一项指标     

Ovarian endometrioid carcinoma with diffuse pigmented peritoneal keratin granulomas: a case report and review of the literature

The presence of keratin granulomas in peritoneal cavity associated with ovarian endometrioid carcinoma, which might be related to leakage from the ovarian tumor, is rarely reported. Its clinical significance has not yet been well investigated. We report a case presenting with intermittent abdominal pain after an acute episode 1 month before a complex adnexal tumor was noted. Comprehensive cytoreductive surgery was performed. The ovarian tumor was an endometrioid adenocarcinoma with squamous differentiation. There were diffuse brownish flecks over the omental surface and pelvic peritoneum, which contained fragments of degenerated squamous cells, keratin, and numerous foreign body giant cells. Extensive multiple sections were examined for these implants. DNA flow cytometry and various immunostaining studies (HER-2/neu, p53, CK-7, and cytokeratin [AE1/AE3]) were performed. Since viable epithelial cells in the implants could be differentially identified against mesothelial or granulomatous components by CK-7 staining and DNA aneuploidy was demonstrated on primary ovarian tumor, four courses of chemotherapy were administered. The patient has been free of disease for 18 months since diagnosis.     

Biochemical and immunohistochemical studies on carcinoembryonic antigen of ovarian mucinous and serous tumors

The carcinoembryonic antigen (CEA) in the cyst fluid of ovarian mucinous and serous tumors was investigated. The molecular weight and antigenicity of the CEA from both ovarian tumors were very similar to those of colon cancer CEA as determined by SDS electrophoresis and double immunodiffusion on agar plates. In the cyst fluid of ovarian mucinous tumors, the amount of CEA was generally high and CEA of molecular weight (MW) 200,000 was increased. In contrast, in the cyst fluid of ovarian serous tumors, the CEA amount was low and CEA variants of MW 370,000 and 180,000 were present in addition to the main CEA of MW 200,000. Immunohistochemically, CEA was stained mainly in the intestinal type epithelium of ovarian mucinous tumors, and the CEA revealed a tendency to be stained more frequently and strongly with increasing degree of tumor malignancy. Thus, ovarian mucinous tumors (especially the intestinal type epithelium) produced large amounts of CEA which closely resembled colon cancer CEA, whereas ovarian serous tumors produced small amounts of CEA, including some CEA variants. In the study of ovarian epithelial tumors, CEA may be useful as a marker for the malignant transformation of ovarian mucinous tumors.     

Cytokeratin staining of resected lymph nodes may improve the sensitivity of surgical staging for endometrial cancer

OBJECTIVE: The presence of metastases to regional lymph nodes (LN) is the single most important risk factor in endometrial cancer. Advances in molecular biology have provided more sensitive methods for detecting micrometastasis. This was a pilot study to determine whether cytokeratin staining of LN from endometrial cancer patients is more sensitive than traditional histopathologic evaluation for the detection of micrometastasis. METHODS: The inclusion criteria included patients with surgical stage I-II endometrial cancer having >50% myometrial invasion, lesions >2 cm, and negative LN together with one of the following: FIGO grade 3 or cervical or lymph-vascular involvement. A matched control group included patients with LN metastasis. The evaluation of the LN at the time of initial surgery consisted of a frozen section and a reevaluation on permanent sections with H&E. In the study, lymphadenectomy specimens were cut, stained again with H&E and with cytokeratin, and examined. Cytokeratin staining was performed with AE1/AE3 antibodies. There were 16 LN-negative cases and 9 LN-positive controls. RESULTS: There was complete agreement between the LN assessment at time of surgery and the study H&E review prior to the staining for cytokeratin. However, 2 LN-negative cases (12.5%) had micrometastasis by cytokeratin staining. One of these patients developed recurrent disease in the para-aortic LN and died of disease at 2.8 years. CONCLUSION: Cytokeratin staining may improve the sensitivity for detection of metastasis compared to traditional evaluation. This study strongly suggests that these micrometastasis are clinically significant. An approach incorporating cytokeratin analysis could improve the risk assessment of specific patients.     

Immunolocalization of epidermal growth factor receptor and c-erbB-2 oncogene product in human ovarian carcinoma.

Abnormalities of epidermal growth factor receptor (EGFR) and c-erbB-2 have been demonstrated to be correlated with aggressive biologic behavior in a variety of human cancers. To analyze the possible roles of these oncogenes in ovarian neoplasms, immunolocalization of EGFR and c-erbB-2 oncogene product was performed in 45 cases of human ovarian mucinous and serous cystadenomas, carcinomas of low malignant potential (LMP), and invasive carcinomas by employing antibodies against these oncogene products. EGFR immunoreactivity was present in 15 of 35 LMP and invasive carcinomas and 1 of 10 cystadenomas. On the contrary, immunoreactivity of p185, which is an oncogene product of c-erbB-2, was detected only in five cases of carcinoma and in no benign cystadenoma. These results indicate that EGFR may be involved in the neoplastic process in epithelial ovarian adenocarcinoma, especially mucinous carcinoma, but involvement of c-erbB-2 is probably not as prevalent as considered previously. Four of the five cases immunohistochemically positive for p185 were also positive for EGFR, which suggests that expression of EGFR and p185 is to some extent correlated in human ovarian carcinoma.     

Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells.

We investigated the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on migration, invasion and proteinase expression of gynecological cultured cancer cells (SKG-IIIb cervical squamous cell carcinoma, OMC-4 cervical adenocarcinoma, SNG-M endometrial adenocarcinoma and OMC-3 ovarian adenocarcinoma), and whether these growth factors affect thymidine phosphorylase/platelet-derived endothelial cell growth factor expression of tumor cells. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatment of tumor cells with EGF and TGF-alpha resulted in the increase of type IV collagenases, stromelysin and urokinase-type plasminogen activator which was partly confirmed by immunoblot analysis. The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor which has angiogenic activity, was also upregulated by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion process of gynecological tumor cells which may be associated with their stimulatory action on the motility of tumor cells, the expression of proteinases secreted by tumor cells and the angiogenic phenotype.     

Urachal adenocarcinoma metastatic to the ovaries: case report and literature review.

We report a urachal adenocarcinoma metastatic to both ovaries in a 50-year-old Japanese woman. Pelvic examination and imaging studies revealed a large cystic tumor occupying the pelvis and another cystic tumor between the umbilicus and the urinary bladder. A laparotomy was performed. Histopathological examination revealed a urachal tumor that was a well-differentiated invasive mucinous adenocarcinoma; the overlying urothelium was intact. The right and left ovarian tumors were well-differentiated mucinous adenocarcinomas. The urachal and ovarian tumors were immunoreactive for cytokeratin 20 and carcinoembryonic antigen, but negative for cytokeratin 7. The patient is alive with lymph node and bone metastases 6 months postoperatively. This is the eighth reported case of an adenocarcinoma of the bladder with ovarian metastasis.     

Intestinal-type cervical adenocarcinoma in situ and adenocarcinoma exhibit a partial enteric immunophenotype with consistent expression of CDX2.

Most cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma are of the usual or endocervical type. However, intestinal types of AIS and adenocarcinoma exist. With an intestinal-type adenocarcinoma in the cervix, the question may arise as to whether one is dealing with a primary cervical neoplasm or direct or secondary spread from an intestinal adenocarcinoma. In organs such as the ovary, urinary bladder, esophagus, and gallbladder, intestinal-type glandular epithelium often expresses enteric markers, but this has hardly been studied in the cervix. The purpose of this study was to investigate whether intestinal-type AIS and adenocarcinoma in the cervix express enteric markers and to ascertain whether these antibodies are of value in the distinction from a metastatic intestinal adenocarcinoma. We compared the immunophenotype of these lesions with that of usual-type AIS and adenocarcinomain the cervix. Cases included were AIS of usual type (n = 6), primary cervical adenocarcinoma of usual type (n = 6), AIS of intestinal type (n = 21), primary cervical adenocarcinoma of intestinal type (n = 3), primary cervical adenocarcinoma with signet ring cells (n = 2), and colorectal adenocarcinoma involving the cervix (n = 5). All cases were stained with cytokeratin (CK) 7, CK20, monoclonal carcinoembryonic antigen (CEA), p16, and CDX2. Staining was categorized as negative, focally positive (<50% cells), or diffusely positive (50% or more cells). Usual-type AIS was always diffusely CK7 positive, typically diffusely CEA and p16 positive, and always CK20 negative. CDX2 was positive in 1 case. All usual cervical adenocarcinomas were diffusely CK7 and p16 positive, and all were immunoreactive with CEA. Five and 2 cases were CK20 and CDX2 positive, respectively. Intestinal-type AIS was diffusely CK7 positive (all cases) and typically CK20 negative and diffusely CEA and p16 positive. All but 1 case exhibited diffuse nuclear positivity with CDX2. In addition, usual-type AIS adjacent to intestinal type was CDX2 positive in 13 of 21 cases. The 3 cases of primary cervical intestinal-type adenocarcinoma were diffusely CK7 positive, focally or diffusely positive with CK20 and CDX2, and focally positive with CEA. One case was diffusely p16 positive, 1 focal and 1 negative. The foci of signet ring cells in the 2 primary cervical adenocarcinomas were diffusely CK7 and p16 positive and negative with CK20 and CDX2. Colorectal adenocarcinomas involving the cervix were typically diffusely positive with CK20, CEA, and CDX2; negative with CK7; and negative or focally positive with p16. Intestinal types of cervical AIS and adenocarcinoma exhibit a partial enteric immunophenotype, usually with diffuse expression of CDX2 and, in some cases, staining with CK20. They maintain their CK7 immunoreactivity and are usually p16 positive. Although there is immunophenotypic overlap, focal staining with CK20 together with diffuse CK7 and sometimes p16 positivity helps to distinguish intestinal types of cervical adenocarcinoma from involvement by a colorectal adenocarcinoma; CEA and CDX2 are of no value in this regard. CDX2 positivity in usual-type AIS adjacent to intestinal type and in occasional cases of pure usual-type AIS may be a reflection of early intestinal differentiation before this is morphologically apparent. Using a set of cases of AIS diagnosed in a single institution over a 7-year period (77 usual type; 13 intestinal type), intestinal type was more likely to be associated with early invasive adenocarcinoma than usual type (31% vs 17%), suggesting that intestinal differentiation may be a risk factor for invasion in premalignant cervical glandular lesions.     

Utility of anti-carcinoembryonic antigen monoclonal antibodies for differentiating ovarian adenocarcinomas from gastrointestinal metastasis to the ovary.

The distinction between primary ovarian tumors and metastatic cancers to the ovary is frequently ambiguous. Recently, we reported that the D-14 monoclonal antibody (MAb), which is directed against a specific epitope of carcinoembryonic antigen (CEA), always reacts with colorectal adenocarcinomas and only rarely with neoplasms of non-gastrointestinal origin [J. Cancer Res. Clin. Oncol. 116, 51-56 (1990)]. We report here an analysis of the reactivity of four different anti-CEA MAbs with formalin-fixed tissue sections of human primary and metastatic colorectal and ovarian carcinomas. The four monoclonal antibodies employed were D-14, CEJ065, ZCEA1, and SP-625. D-14, CEJ065, and SP-625 MAbs reacted with essentially every colorectal adenocarcinoma. In contrast, ZCEA1 was the least reactive and 10 tumor samples showed no reactivity to this MAb. All four anti-CEA MAbs demonstrated scarce immunoreactivity with ovarian carcinomas and appear to be useful for distinguishing between ovarian carcinoma and colorectal metastasis to the ovary. Adenocarcinomas of the stomach and breast were also examined to determine CEA reactivity with the D-14 MAb, since these tumors need to be considered in the differential diagnosis of an ovarian mass. The majority of stomach adenocarcinomas were immunoreactive. In contrast, only 3 of 36 breast carcinomas were weakly immunoreactive, indicating that D-14 MAb is of no assistance in identifying breast carcinoma metastasis to the ovary.     

Expression of cytokeratins in granulosa cell tumors and ovarian carcinomas

Summary One of the problems in histopathology of ovarian tumors is differential diagnosis between the poorly differentiated carcinomas and granulosa cell tumors of the sarcomatoid type. Hence we evaluated the expression of various cytokeratins (CK 1–19; CK 10, 13, 14, 15, 19; CK 8, 18, 19; CK HMW 1, 5, 10, 11; CK 8; CK 1–19 St?hli; CK AE1/AE3) immunohistochemically in 53 ovarian malignancies (11 of them poorly differentiated carcinomas and 12 granulosa cell tumors). CK HMW was not detected in granulosa cell utmors, and in only half of the carcinomas. AE1/AE3 was expressed by more than 90% of ovarian carcinomas but by one granulosa cell tumor only. The other keratins we investigated showed higher expression rates in granulosa cell tumors and/or lower expression rates in ovarian carcinomas. We think that cytokeratin immunohistochemistry is of value in differentiating between granulosa cell tumors and ovarian carcinomas.     

Endometrial adenocarcinoma with osteoclastic giant cells in stroma: a case report and review of literature

It is rare to find osteoclastic giant cells (OGCs) as a stromal reaction in uterine adenocarcinoma of endometrium. Here, we report a case of a 60-year-old female diagnosed with adenocarcinoma of endometrium. Total hysterectomy with bilateral salpingo-oopherectomy and removal of pelvic lymphnodes was performed. Histologically, the tumour showed adenocarcinoma of the endometrium with mucin secretion. The stroma showed some plump reactive pleomorphic cells, resembling stromal cells, infiltrated uniformly with OGCs and mononuclear cells (MNCs). The epithelial cells of adenocarcinoma stained positive for cytokeratin (CK 7) (CAM 5.2). The osteoclastic giant cells and mononuclear cells stained positive with CD68 and negative with cytokeratin and vimentin. We conclude that the osteoclastic giant cells originated from reactive histiocytes/monocytes as a stromal reaction to malignancy.     

Nuclear survivin expression is a positive prognostic factor in taxane-platinum-treated ovarian cancer patients

Objective

Study of the hen immune system led to seminal contributions to basic immunological principles. Recent studies of spontaneous ovarian cancer in the laying hen show strikingly similar tumor types and antigen expression compared to human ovarian cancer, suggesting hens would be valuable for studies of tumor immunology and pre-clinical vaccine development. Circulating mesothelin is a relatively specific marker for human ovarian cancer and autoantibodies to mesothelin were reported. We hypothesized that hen tumors express mesothelin and that circulating anti-mesothelin antibodies occur in response to tumors.

Methods

Mesothelin mRNA expression was analyzed by RT-PCR in hen ovarian tumors and normal ovaries. Mesothelin protein expression was evaluated by immunohistochemistry (IHC) and two-dimensional SDS-PAGE Western blots. Anti-mesothelin antibodies were assessed by immunoassay of sera from hens with normal ovaries and with ovarian tumors.

Results

Significant mesothelin mRNA expression was observed in 57% (12/21) of hen ovarian tumors but not in normal ovaries and was found predominantly in serous tumors as in humans. Mesothelin protein was detected in tumors with mesothelin mRNA by IHC and 2D Western blots, but not in normal ovaries or tumors without mesothelin mRNA. Circulating anti-mesothelin antibodies occurred in 44% (n = 4/9) of hens with ovarian tumors which express mesothelin mRNA and were not found in hens with tumors that did not express mesothelin (n = 0/5) or normal ovaries (n = 0/5).

Conclusion

The results support the utility of the hen as a novel model for preclinical studies of mesothelin as a biomarker and a target for immunotherapy.