A panel of immunohistochemical stains, including carcinoembryonic antigen, vimentin, and estrogen receptor, aids the distinction between primary endometrial and endocervical adenocarcinomas.

The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma.     

Detection of carcinoembryonic antigen of endometrial carcinoma and hyperplasia

The amount and distribution of carcinoembryonic antigen (CEA) was determined in 41 cases of endometrial carcinoma and 23 cases of endometrial hyperplasia using the Avidin-biotin-peroxidase-complex technique. The surface location and amount of CEA in cancer specimens were found to be related to the histological differentiation of tumor. In endometrial hyperplasia, the content of CEA was the same as that of cancer, but the surface location was different.     

Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: another viewpoint.

Several studies have reported on the use of antibodies to monoclonal carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably enthusiastic results. It is still unclear whether site of origin or pathway of differentiation (endometrioid [em] versus mucinous [m]) is more important in predicting immunohistochemical differences. In the present study, paraffin blocks from adenocarcinomas of known origin were retrieved and immunostained with monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20, estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors with mixed patterns received separate scores for the em and m foci). Mean CEA scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1, and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6; PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20, 0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with the latter more important for VIM and PR, the former for ER, both for CEA (only mEC was frequently strongly positive), and neither for the CKs studied. No one stain or combination reliably distinguished endometrial from endocervical origin. The only immunostaining pattern that might identify a site of origin with more accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in this series an endometrial origin of the tumor.     

Immunohistological study of isoantigens, carcinoembryonic antigen and human chorionic gonadotropin in adenocarcinomas of the uterus

Isoantigens, carcinoembryonic antigen (CEA) and human chorionic gonadotropin (hCG) were simultaneously studied by immunohistology in the cervical and endometrial adenocarcinomas. Isoantigen loss was observed in all adenocarcinoma in situ (AIS) of the uterus. However, they appeared again in some tumor cells in 8 of 23 cervical and 4 of 41 endometrial adenocarcinomas. CEA was positive in 1 of 4 AIS and 22 of 23 adenocarcinomas of the cervix. It was distributed continuously in the apical portion and/or in the whole cytoplasm of tumor cells. On the other hand, CEA was positive only in 16 of 41 endometrial adenocarcinomas. It was strongly positive in the squamous elements, but weakly and sparsely in the apical portion and/or in the cytoplasm of some isolated glandular cells which occasionally showed a tendency to squamous differentiation. The majority of neoplastic glands, however, were negative for CEA. HCG was positive in 1 of 23 cervical and 3 of 41 endometrial adenocarcinomas. Two or 3 antigens were found concomitantly in some tumors, but localized differently from each other. It was concluded from the present study that the simultaneous examination of multiple antigens may be useful for characterization of adenocarcinomas of the uterus.     

Immunohistochemical demonstration of carcinoembryonic antigen and ultrastructural features of endometrial adenocarcinoma

Determination of carcinoembryonic antigen levels in plasma (45 cases) and the immunohistochemical demonstration of tumor CEA (37 cases) were carried out in patients with endometrial adenocarcinoma. Twenty four out of 37 were also studied with the electron microscope. The plasma CEA level prior to therapy was significantly elevated (greater than 5.0ng/ml) in only one case (1/45:2.2%) of endometrial adenocarcinoma. CEA levels were more consistently elevated (4/17:23.5%) in patients with cervical adenocarcinoma. Immunoperoxidase staining of CEA (PAP method) was carried out using formalin-fixed paraffin embedded sections of 37 tumors. Tissue CEA activities were found in 9 out of 37 endometrial adenocarcinomas (24.3%) and 19 of 23 cervical adenocarcinomas (82.6%). Immunoreactive CEA was present in a high concentration on the cell surface of endometrial glands and less dense in their cytoplasm. In 9 of CEA positive endometrial carcinoma tissues, squamous metaplastic lesions were found in 4 cases and mucinous metaplasia in one case which were all CEA positive. With regard to the histopathological grade, CEA positive specimens were categorized G1 (4) and G2 (5) and all of the G3 were CEA negative. Seven of 9 cases of CEA positive specimens were examined under the electron microscope. There was no definite tendency in their ultrastructural characteristics, but all of the specimens examined revealed abundant cytoplasmic organelles suggestive of intracytoplasmic differentiation analogous to those of endometrial cells in proliferative phase. Moreover, fine structures of squamous and mucinous metaplastic cells were also described in detail.     

子宫内膜癌患者血清CP2、CA125、唾液酸和癌胚抗原检测的临床意义

目的探讨肿瘤标志物CP2、CA125、唾液酸（SA）和癌胚抗原（CEA）检测对子宫内膜癌患者的临床意义。方法选取154例具有肿瘤标志物检测结果的子宫内膜癌患者的临床病理资料进行回顾性分析。结果子宫内膜癌患者血清CP2、SA、CA125和CEA水平升高的百分率分别为23．4％、36．8％、19．0％和30．3％。血清CP2水平升高与手术病理分期、病理分化程度、附件受累、腹腔细胞学检查阳性及盆腔淋巴结转移相关（P值分别为0．002、0．040、0．019、0．019、0．005）;血清SA水平升高与附件受累、腹腔细胞学检查阳性相关（P值分别为0．021、0．000）;血清CA125水平升高与病理分化程度、宫颈受累和盆腔淋巴结转移相关（P值分别为0．014、0．006、0．018）;CEA与各临床病理特征间均无相关性（P均〉0．05）。血清CP2、CA125和CEA水平升高与患者预后相关（P值分别为0．016、0．000、0．016）,其中CA125水平与预后关系最为密切。结论子宫内膜癌缺乏特异性肿瘤标志物,CP2与子宫内膜癌临床病理特征相关性较强,CP2、CA125和CEA对患者预后有提示作用。     

Value of endocervical curettage in the staging of endometrial carcinoma

The prognosis for women with endometrial cancer correlates with stage of disease. Spread to the cervix distinguishes Stage II from Stage I disease. To assess the accuracy of endocervical curettage (ECC) in predicting cervical involvement by endometrial adenocarcinoma, we examined and assigned to one of four groups the ECC from 147 women treated between 1980 and 1985. Ultimate determination of spread to the cervix was based on examination of subsequent hysterectomy specimens. In the hysterectomy specimen 19 of 147 women (13%) had cervical involvement demonstrated. Five women had tumor clearly within the endocervical tissue of the ECC (Group I), and three of these five (60%) had spread of tumor to the cervix in the hysterectomy specimen. At hysterectomy, 13 of 41 women (32%) with tumor present but not contiguous with endocervical tissue within the ECC (Group II) had cervical involvement. Of the 80 women without tumor in the curettage (Group III), one (1.2%) had cervical involvement by tumor at hysterectomy. Two of the 21 women (9.5%) with curettings considered insufficient for diagnosis (Group IV) had spread of adenocarcinoma to the cervix within the hysterectomy specimen. We also compared the results of ECC performed at our institution with those performed at referring hospitals and found a significant difference between them in ability to obtain definitive results. We conclude that (a) the absence of carcinoma in ECC is highly predictive of absence of cervical involvement by endometrial carcinoma; (b) ECC having tumor within endocervical tissue is a good predictor of cervical involvement by tumor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical investigation of vimentin of uterine endometrial and endocervical adenocarcinoma

We investigated the localization and the immunoreactivity (IR) of vimentin in normal and cancerous glandular epithelia of the uterine corpus and cervix. The materials for the study were 33 cases of endometrial adenocarcinoma, 21 cases of endocervical adenocarcinoma, and 12 cases of uterine myoma which had normal endometrium and cervix. A similar study was also performed on smear materials. In normal endometrium, the vimentin was localized not only in the stromal cells but also in the epithelial cells. The IR of the vimentin in the epithelial cells was more prominent in the proliferative phase than in the secretory phase. On the other hand, in normal cervix, the vimentin was not localized in the epithelial cells. In endometrial adenocarcinoma, the IR of the vimentin was markedly or moderately positive in more than half of the cases. In endocervical adenocarcinoma, the IR of the vimentin was absent in all but 2 cases which were of the endometrioid type. The vimentin IR of the stromal cells was clearly observed in endocervical as well as endometrial adenocarcinoma. Very similar results were observed in the smear materials. In endometrial adenocarcinoma, the differentiation, the depth of myometrial invasion and the lymph node metastasis were regarded as the prognostic factors, and the vimentin IR appeared more intensive in the cases of well differentiated and superficial myometrial invasion. The above results showed that there was a remarkable difference between endometrial and endocervical epithelial cells in the vimentin IR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum carbohydrate antigen elevations in endometrial adenocarcinomas: characterization of DU-PAN-2 expression as a tumor marker

AIM: To characterize serum elevations of carbohydrate antigens; DU-PAN-2, CA19-9, sialyl Lewisx and CA125 in endometrial adenocarcinomas (EMACs), particularly focusing on the clarification of DU-PAN-2 expression profiles. METHODS: Sixty-four resected EMACs of endometrioid type were used. The preoperative serum values of four markers were measured and comparatively analyzed regarding the relationship between histological grade and clinicopathological stage. RESULTS: The overall ratios of positive cases were 26.2% for DU-PAN-2, 25.0% for CA19-9, 13.6% for sialyl Lewisx, and 35.5% for CA125. DU-PAN-2 decreased as the grading went up (G1: 410.3 +/- 243.8 to G3: 246.7 +/- 90.0 U/mL), however, the reverse was true with CA19-9 (G1: 123.9 +/- 147.4 to G3: 320.0 +/- 180.0 U/mL). Sialyl Lewisx showed a strong tendency towards high elevation in G1 (346.3 +/- 102.6 U/mL), compared to G3 (< 2.5 U/mL). CA125 increased markedly as the grading went up (G1: 43.5 +/- 6.3 to G3: 578.0 +/- 10.0 U/mL). During staging-up from I + II to III + IV, the positive ratios inclined in all four markers as follows: DU-PAN-2, 18.4-53.3%; CA19-9, 20.4-40.0%; sialyl Lewisx, 11.4-22.2%; CA125, 31.8-44.4%. Serum elevations and positive ratios were correlated for DU-PAN-2, CA19-9 and CA125, while the reverse relationship was found for sialyl Lewisx. CONCLUSION: It is suggested that DU-PAN-2 tends to be produced more in well-differentiated components of EMACs than in poorly differentiated ones. Since approximately half the cases with EMAC were serologically positive for DU-PAN-2 in stage III + IV, the marker is believed to be of much use for monitoring the cases with an extrauterine extent.     

Evaluation and staging of endometrial and endocervical adenocarcinoma by contact hysteroscopy

Contact hysteroscopy is a new technique for examining the uterine cavity and endocervical canal to aid in the diagnosis and staging of neoplasia. Direct visual examination of the endometrium may be accomplished without any distending medium and regardless of the presence of bleeding. The contact endoscope does not require any light source other than ambient room light because of an ingenious light trap which is built into the instrument. Fifteen cases of adenocarcinoma of the endometrium and endocervix are described in which contact hysteroscopy aided in identification, localization, and definition of spread of the tumors.     

Expression of carcinoembryonic antigen and ferritin in normal, hyperplastic, and neoplastic endometrium

The distribution of carcinoembryonic antigen (CEA) and ferritin was demonstrated by immunohistochemical method in 95 patients with normal, hyperplastic, and neoplastic endometrium in order to distinguish among these conditions. Fifteen patients with normal endometrium (NE), 28 with hyperplasia (AH), 12 with atypical hyperplasia (AAH), and 40 with endometrial carcinoma (CA) were studied. Paraffin section tissues were subjected to immunostaining according to the avidin-biotin complex method. CEA was found in 33% of NE cases, 46% of AH, 75% of AAH, and 83% of CA (P less than 0.01). Ferritin was not detected in any case of NE; however, it was detected in one case (4%) of AH, in one case (8%) of AAH, and in 88% of CAs (P less than 0.001). Both tumor markers exhibited a heterogeneous staining pattern, and for a given histologic hyperplastic or malignant lesion, corresponded to several phenotypes. There was no significant correlation between clinical stage or tumor grade and CEA or ferritin expression. In conclusion, ferritin seems to be a better biological marker than CEA in distinguishing between hyperplastic and neoplastic endometrial lesions and it is also more reliable than CEA for endometrial malignancy since it was absent in normal and hyperplastic endometria.     

Reappraisal of endocervical curettage in predicting cervical involvement by endometrial carcinoma

Determining if there is cervical invasion by endometrial carcinoma is critical to both staging and therapy. The dependability of endocervical curettage (ECC) in the staging of endometrial cancer is seldom subject to review. This study appraised this dependability. The results indicated that the dependability of ECC in assessing cervical invasion by endometrial cancer is in serious question. Making the determination solely on the basis of ECC would result in the overtreatment of six of seven patients with positive ECC. In view of this high false-positive rate, direct visual inspection and biopsy of the endocervical canal with endoscopy might be warranted before definitive therapy.     

C-kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance.

The proto-oncogene c-kit is a transmembrane-tyrosine-kinase receptor that is structurally related to the platelet-derived growth-factor receptor (PDGFR) and is involved in cell differentiation. C-kit has been found to be expressed in certain solid tumors and may play a role in their tumorigenesis. Recently, a tyrosine-kinase inhibitor specific for the PDGFR family, bcr-abl, and c-kit (STI571) has been reported to have therapeutic effects in tumors expressing the aberrant forms or high quantities of target proteins. Expression of c-kit has not been well evaluated in endometrial adenocarcinomas. In this study, c-kit immunoreactivity was evaluated on paraffin sections of 72 endometrial adenocarcinomas (57 endometrioid, 10 serous, and 5 clear cell) with a polyclonal antibody. Immunoreactivity of c-kit was analyzed semiquantitatively and correlated with various clinicopathologic factors. Cytoplasmic c-kit immunoreactivity was detected in 42 (58%) tumors. Thirty-four (60%) endometrioid, 8 (80%) serous, and 0 of the 5 clear-cell adenocarcinomas were c-kit positive. There was a significant correlation between c-kit positivity and the depth of myometrial invasion. Patients with c-kit-positive endometrial adenocarcinomas more frequently had metastases and shorter disease-free survival. Expression of c-kit may be a potentially adverse prognostic feature in endometrial adenocarcinoma. Patients with c-kit-positive advanced endometrial adenocarcinoma might benefit from tyrosine-kinase-inhibitor therapy.     

Electron microscopical and immunohistochemical study of human endometrial carcinoma with special reference to localization of estrogen receptors and carcinoembryonic antigen

Human endometrium, endometrial hyperplasia and endometrial carcinoma were observed by light microscope. Endometrial carcinoma was histologically divided into Grade I (53 cases), Grade II (10 cases), and Grade III (7 cases). According to the results of electron microscopical analysis, cancer cells in GIII were smaller and showed a higher N/C rate and less mitochondria in the cytoplasma than those of GI and GII. Rough endoplasmic reticula were well developed in GI and GII compared with GIII. Immunohistochemically, ER localized in 54% cases of endometrial carcinoma, and decreased in positive rates of undifferentiated carcinoma. The metaplastic area in carcinoma showed the localization of ER and CEA. A close correlation between ER and CEA was demonstrated in endometrial carcinoma. Ultrastructurally, rough endoplasmic reticula were well developed in the cytoplasma of cancer cells in the strong positive cases of ER and CEA. It has been proved that histological detection of ER and CEA in endometrial carcinoma is very important in deciding the diagnosis, prognosis and therapy.