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.     

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.     

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.     

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.     

The distribution of mucins, carcinoembryonic antigen, and mucus-associated antigens in endocervical and endometrial adenocarcinomas

The presence and distribution of mucins, carcinoembryonic antigen (CEA), and mucus-associated antigens M1, M2, and M3 were investigated in 22 normal endocervices, 25 normal endometria, 25 endocervical adenocarcinomas, and 32 endometrial adenocarcinomas to determine their contribution in the differential diagnosis of endocervical and endometrial adenocarcinoma. Sections of formalin-fixed paraffin-embedded tissues were stained with conventional histochemical stains such as d-PAS and Alcian blue to investigate the distribution of mucins. For the demonstration of CEA and the mucus-associated antigens an indirect immunoperoxidase technique was used. In the present study d-PAS and Alcian blue stains, as well as immunohistochemistry of CEA, did not contribute to the discrimination between adenocarcinomas of the endocervix and endometrium. Immunohistochemistry of mucus-associated antigens showed a positive reaction of M3 in the majority (68%) of the endocervical carcinomas. In contrast, if foci of endocervical-type metaplasia were excluded, M3 was absent in tumor cell cytoplasm of endometrial adenocarcinomas. Furthermore, the expression of M2 without the presence of the other mucus antigens in tumor cell cytoplasm, as seen in 24% of the endometrial adenocarcinomas, was never found in endocervical adenocarcinomas.     

Evaluation of PTEN expression in cervical adenocarcinoma by tissue microarray

PTEN, a tumor suppressor gene, appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell proliferation and cell survival. Somatic PTEN mutations are involved in a variety of tumors, including endometrial carcinomas, where PTEN expression is diminished. We examined expression of PTEN in a series of cervical adenocarcinomas and precursors, using tissue microarray (TMA) technology. TMA blocks were constructed using paraffin-embedded, formalin-fixed tissues from 273 samples derived from 16 normal cervical biopsies, 119 cases of invasive adenocarcinoma, and 20 high-grade cervical glandular intraepithelial neoplasia (CGIN). Fresh 3-mum sections were cut and immunostained with PTEN, and expression was correlated with clinicopathologic variables, including histologic subtypes of adenocarcinoma. In 137 patients, PTEN expression was positive in 121 (88%). The intensity and distribution of PTEN staining in the tumor tissue were more heterogeneous than those observed in the normal tissues. There were no significant differences in distribution or intensity of PTEN expression between adenocarcinoma in situ and subtypes of invasive adenocarcinoma. Our findings show that unlike the case in most endometrial carcinomas, PTEN expression is retained during the process of carcinogenesis in the glandular cervix. There is, however, evidence of altered distribution and intensity of PTEN expression in cervical adenocarcinoma cells.     

胰岛素样生长因子-1受体在子宫内膜癌中的表达及临床意义

目的 研究子宫内膜癌组织中IGF-1R的分布、表达及其临床意义。方法 选取30例子宫内膜癌手术标本，石蜡切片，采用PV-600PicTureTM检测试剂进行免疫组化，测定IGF-1R的分布及表达，分析与临床病理之间的关系。另取10例正常的增生期子宫内膜标本作为对照。结果 IGF-1R为膜受体。IGF-1R在10例正常增生期子宫内膜细胞中的阳性表达率为70％，无过度表达；而在30例子宫内膜癌细胞中的阳性表达率为90％，过度表达率为40％（中度阳性7例、强阳性5例）。统计表明，正常增生期子宫内膜细胞与子宫内膜癌细胞相比IGF-1R阳性表达率差异尤显著性（P=0．13）；IGF-1R过度表达率差异有显著性（P=0．017）。子宫内膜癌细胞膜IGF-1R阳性表达及过度表达在高分化与中、低分化之间有显著差异（与分级呈负相关系：分化越低，IGF-1R的表达越强，反之，分化高，IGF-1R的表达则弱）。IGF-1R的阳性表达及过度表达在临床分期Ⅰ-Ⅲ期各组间均无明显差异。结论 IGF-1R在子宫内膜癌细胞膜表达，且随恶性程度的增加其表达量增加，IGF-1R的表达量可以预测内膜癌的预后，对临床治疗可能具有一定的指导意义。     

Increased incidence of adenocarcinoma of uterine cervix.

A greater than expected incidence of adenocaricinoma of the uterine cervix is reported. Among 41 cases of cervical carcinoma, 14 (34%) were adenocarcinoma. Clinicopathologic data for these cases are summarized. Eleven of the 14 cases were pure adenocarcinomas; 3 were mixed adenosquamous carcinoma. The value of cytopathology is demonstrated in the 7 of 9 pretreatment cervical cytologies whereby adenocarcinoma was indicated (an accuracy rate of 78%). The other 2 revealed abnormal cells in which malignancy was a possibility. Three cases clinically were initially considered endometrial adenocarcinoma, but by our classification criteria, including Alcian blue staining for cervical mucin content of acid mucopolysaccharide, they were more specifically identified as primary endocervical in origin.     

Expression of tumor suppressor gene product p14ARF in endometrioid adenocarcinoma of the uterine corpus.

p14 activates p53 by inhibiting MDM2 expression and arrests the cell cycle in G1 and G2/M. Abnormal p14 expression has been reported in various human cancers. This study investigated p14 expression in endometrioid adenocarcinoma of the uterine corpus in an attempt to clarify its correlation with other cell cycle-regulators and clinicopathologic parameters. The specimen studied consisted of 124 endometrioid adenocarcinomas, 20 normal endometria, and 20 endometrial hyperplasias. Immunohistochemical staining of formalin-fixed and paraffin-embedded tissues was performed using a Catalyzed Signal Amplification System. Cells with >5% positive staining were classified as positive for p14. A staining score of 1 was adopted when the percentage of positive nuclei was <5%, a score of 2 when it was 5 to 50%, and a score of 3 when it was >50%. In normal endometrium, the frequency of positive staining in the proliferative phase and secretory phase was 50% (4/8) and 58.3% (7/12), with staining scores of 1.8+/-0.9 and 1.6+/-0.5, respectively. The frequency of staining in simple hyperplasia (SH), complex hyperplasia (CH), and complex atypical hyperplasia (CAH) was 88.9% (8/9), 25% (1/4), and 42.9% (3/7), respectively; the staining scores were 1.9+/-0.3, 1.3+/-0.5, and 1.4+/-0.5, respectively. Among endometrioid adenocarcinomas, the frequency of staining of well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) adenocarcinomas was 69% (49/71), 64% (16/25), and 42.9% (12/28) respectively, with staining scores of 2.1+/-0.8, 2+/-0.9, and 1.8+/-1, respectively. Thus expression levels of p14 were higher in G1 tumors than in normal endometria or endometrial hyperplasias, and the frequency of its staining in endometrioid carcinomas was inversely correlated with histologic grade. The staining score for endometrioid adenocarcinomas also was inversely correlated with the labeling index (LI) of Ki-67, but not with that of cyclin A, cyclin D1, cyclin E, cdk2, p27, p53, or other clinicopathologic parameters. In conclusion, p14 expression correlated with histologic grade and Ki-67, but not other prognostic factors in endometrioid adenocarcinoma. Long-term follow-up studies are needed to analyze the significance of p14 expression in these tumors.     

Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix.

The reactivities of new monoclonal antibody 1C5 and anti-carcinoembryonic antigen (CEA) were determined immunohistochemically in 4 adenocarcinomas in situ, 20 invasive adenocarcinomas of various types, and 6 adenosquamous carcinomas of the uterine cervix, as well as in 10 endometrial adenocarcinomas and 10 normal cervices. Among the invasive adenocarcinomas, 90% were positively stained by 1C5 and 55% stained for CEA. Three of four in-situ adenocarcinomas were positively stained by 1C5 and two of four were positively stained by anti-CEA. All adenosquamous carcinomas were stained by 1C5 and four of six stained for CEA. Invasive adenocarcinomas always stained more intensely with 1C5 than did noninvasive lesions in the same specimen. Poorly differentiated adenocarcinomas were stained as strongly with 1C5 as were well-differentiated tumors, but CEA was less effective in identifying poorly differentiated lesions. 1C5 was also more useful than CEA was in distinguishing glandular from squamous neoplastic differentiation, and also appears to be useful in distinguishing endocervical from endometrial differentiation.     

In situ adenocarcinoma and squamous carcinoma of uterine cervix. Pathological and immunohistochemical analysis with cytokeratin 13

OBJECTIVES: The aim of the study was the pathological and immunohistochemical analysis of cytokeratin 13 (CK13) in intraepithelial cervical tumors. STUDY DESIGN: We studied 415 in situ squamous carcinomas and 13 in situ mucinous cervical type adenocarcinomas of the uterine cervix. All patients underwent laser cervical conization and had a follow-up ranging 12-135 months. RESULTS: 3% of the squamous carcinoma patients recurred during the follow-up period, while the percentage of recurrence of in situ adenocarcinoma patients was 7.6%. We observed positive surgical edges in 46.1% of glandular tumors, and in 5% of squamous tumors. The percentage of recurrence was high among the cases with positive borders independently from their histopathologic type (14.3% in the squamous carcinomas versus 50% in the adenocarcinomas), compared to cases with negative edges (2.3% in the squamous carcinomas versus 0% in the adenocarcinomas). We observed CK13 positive staining in cervical squamous tumors and in mucinous cervical type adenocarcinomas, while there was no positive staining in non-neoplastic cervical glandular elements. CONCLUSION: CK13 positive immunostaining among in situ squamous and in situ mucinous cervical type adenocarcinoma cases adds additional evidence to data supporting a common origin of the two lesions.     

子宫内膜癌手术前分段诊断性刮宫

目的 评价分段诊断性刮宫（分段诊刮）对判断子宫内膜癌的组织类型以及判断宫颈是否受累的价值。方法 对６９１例子宫内膜癌术前均行分段诊刮,并对分段诊刮和手术切徐标本的病理诊断结果进行比较分析。根据肿瘤与颈管的组织学关系不同,将颈管刮出物分为４型：Ⅰ型即肿瘤组织完全与颈管组织分离;Ⅱ型即肿瘤与颈管上皮相连;Ⅲ型即肿瘤润宫颈间质;Ⅳ型即标本中仅见肿瘤组织。结果 ⑴分段诊刮与手术切除标本病理诊断为子宫内膜癌     

CXCR4 expression is associated with pelvic lymph node metastasis in cervical adenocarcinoma

The aim of this study is to investigate the expression of CXCR4 receptor in cervical adenocarcinoma and related mechanisms involved in pelvic lymph node metastasis. Immunohistochemistry was used to evaluate the expression of CXCR4 and the association of pelvic lymph node metastasis in archived tissue from clinical stage IB cervical adenocarcinomas (n = 37) and from benign specimens obtained at hysterectomy for other causes (n = 48). The HeLa cell (cervical adenocarcinoma-derived cell) line that expresses CXCR4 was used to study the interaction between the CXCR4 receptor and stromal cell-derived factor 1alpha (SDF-1alpha). Cell migration assays, cell numbers, flow cytometry, cell proliferation assay, and western blot were used to study the function of CXCR4 and its downstream signal transduction. The positive cases were semiquantitatively divided into three score classes according to their staining. Tumors with strong CXCR4 stainings were more likely to have pelvic lymph node metastasis than those with weak or negative stainings (87.5% vs 34.5%; P = 0.014). Only 25% of the benign specimens had weak or negative staining for CXCR4. Functioning CXCR4 receptor was expressed on HeLa cells. SDF-1alpha provoked significant signal transduction events, including chemotaxis and rescue from apoptosis. These actions were apparently mediated by the activation and phosphorylation of the extracellular signal-regulated kinase 1/2 and AKT pathways. We conclude CXCR4 expression is associated with cervical adenocarcinoma cell migration and proliferation, and primary cervical adenocarcinoma cells expressing CXCR4 are significantly more likely to metastasize to pelvic lymph nodes.     

The production and characterization of monoclonal antibody, 1C5, reactive with cervical adenocarcinoma of the uterus

A new monoclonal antibody, 1C5, was produced by fusion of spleen cells obtained from mice immunized with CAC-1, a human cell line of cervical adenocarcinoma of the uterus, and NS-1 myeloma cell. The objectives of this study were to obtain moAb that can be used for routine histology and cytology, and to examine the histogenesis of cervical adenocarcinoma. 1. 1C5 reacted with 88% of cervical adenocarcinoma of the uterus, but did not react with cervical squamous cell carcinoma of the uterus and other squamous cell carcinoma. However, 1C5 reacted with some adenocarcinomas, such as endometrial carcinoma of the uterus and ovarial carcinoma. 2. The staining pattern by 1C5 was different, in cervical adenocarcinoma from that in endometrial carcinoma of the uterus, and also different in the endocervical type from that in the endometrioid type of cervical adenocarcinoma. Therefore, 1C5 is useful in distinguishing between two types of adenocarcinoma of the uterus. 3. 1C5 did not react with normal squamous cells or normal columnar cells of the uterine cervix, or with normal endometrial cells of the uterus. However, the columnar cells in a limited area of the squamocolumnar junction were strongly stained with 1C5. 4. 1C5 reacted with ethanol-fixed, and routine formalin-fixed and paraffin-embedded tissue. Thus, 1C5 may be used for clinical diagnosis. 5. 1C5 was found to be IgG1. 6. The molecular weight of the 1C5-defined antigen was 26,000 daltons, and the epitope of the 1C5-defined antigen was carbohydrate moiety. 7. We examined the histogenesis of cervical adenocarcinoma of the uterus by utilizing the reactivity of 1C5.(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical significance of tumor-associated antigen RCAS1 expression in the normal, hyperplastic, and malignant uterine endometrium

OBJECTIVE: A tumor-associated antigen, RCAS1, is recognized by 22-1-1 monoclonal antibody. It was found in carcinomas derived from the uterus and ovary and was especially strongly expressed in invasive cancers. A previous investigation showed the RCAS1 expression to be correlated with a poor prognosis in uterine cervical adenocarcinoma. In this study, we examined whether the expression of RCAS1 is associated with the progression of the uterine endometrial neoplasms. METHODS: The expression of RCAS1 was evaluated by an immunohistochemical analysis. The tissue specimens used in this study included 46 cases of normal uterine endometrium, 40 cases of hyperplasia, and 121 cases of adenocarcinoma. The relationship between RCAS1 expression and several clinicopathological variables (clinical stage, histology, grade, myometrial invasion, lymph-vascular space invasion, and lymph node metastasis) was also assessed in endometrial adenocarcinoma. RESULTS: RCAS1 was positive in 26% of the normal uterine endometrium specimens (12 of 46 total cases), in 32% of the hyperplasia specimens (13 of 40 total cases), and in 68% of the adenocarcinoma specimens (83 of 121 total cases). As a result, the expression of RCAS1 was statistically higher in adenocarcinoma than in the normal and hyperplastic endometrium (P < 0.0001). RCAS1 was statistically detected more frequently in grade 3 than in grade 1 or 2 (P < 0.05); however, there was no correlation between the antigen expression and the clinical stage, myometrial invasion, lymph-vascular space invasion, or lymph node metastasis. CONCLUSION: RCAS1 expression might thus be associated with the malignant transformation and poor differentiation observed in uterine endometrial adenocarcinoma.     

Immunohistochemical characterization of endocervical papillary serous carcinoma

Abstract.   Nofech-Mozes S, Rasty G, Ismiil N, Covens A, Khalifa MA. Immunohistochemical characterization of endocervical papillary serous carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 286–292.
Endocervical adenocarcinomas are rare and aggressive neoplasms. Papillary serous endocervical adenocarcinomas are the rarest form of endocervical adenocarcinomas. This tumor exhibits morphologic similarities to its counterparts commonly seen in the endometrium, fallopian tubes, ovaries, and peritoneum, which are known to have an aggressive behavior. Because of the rarity of this tumor, little is known about its immunophenotyping. In this study, we included ten cases of papillary serous carcinomas arising from the uterine cervix (PSCC) diagnosed in the absence of a primary endometrial malignancy. We studied their immunohistochemical profile, using a panel of antibodies against Ki67, bcl-2, p53, carcinoembryonic antigen (CEA), and CD10, and compared them to 20 consecutive cases of cervical adenocarcinoma of conventional cell subtypes (CAC) (15 mucinous, 3 adenosquamous, and 2 endometrioid). Immunostaining was recorded semiquantitatively. Patients with PSCC ranged in age from 27 to 79 years (mean = 51.6 ± 19.1), while the conventional cell subtypes control group were 28–90 years old (mean = 47.5 ± 16.9). Only p53 and CEA immunostaining significantly correlated with the PSCC morphology ( P = 0.001 and P = 0.016, respectively) as shown by Cochran–Mantel–Haenszel Statistics (Modified Ridit Scores). PSCC is a distinctive immunophenotypic subtype of endocervical adenocarcinoma with significantly higher p53 and lower CEA reactivity than other more common histologic subtypes.     

CD56 expression in ovarian granulosa cell tumors, and its diagnostic utility and pitfalls

OBJECTIVE: The purpose of this study is to investigate CD56 staining in ovarian granulosa cell tumor and its morphological mimics in order to determine the value of CD56 staining in a diagnostic setting. MATERIALS AND METHODS: Tissue samples taken from 82 ovarian tumors, 26 extra-ovarian tumors and 11 normal ovaries were immunohistochemically stained using monoclonal anti-CD56 antibody. Ovarian tumors comprised 32 granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 6 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 17 endometrioid adenocarcinomas and 9 poorly differentiated serous adenocarcinomas. Extra-ovarian tumors comprised 22 uterine endometrial stromal sarcomas and 4 pulmonary small cell carcinomas. Normal ovaries contained 47 ovarian follicles. RESULTS: All of the 32 granulosa cell tumors, all of the 3 Sertoli-stromal cell tumors, all of the 4 small cell carcinomas, 1 of 1 large cell neuroendocrine carcinoma, 11 of 14 fibrothecomas, 5 of 6 carcinoid tumors, 17 of 22 endometrial stromal sarcomas and 7 of 9 poorly differentiated serous adenocarcinomas were positive for CD56. No immunoreactive cells were observed in 17 endometrioid adenocarcinomas or 47 ovarian follicles. All the immunoreactive cells showed membranous staining except for fibrothecomas where vague cytoplasmic staining was seen. CONCLUSION: CD56, known as a neuroendocrine marker, is a sensitive marker of granulosa cell tumors, but since granulosa cell tumors and neuroendocrine tumors may be morphologically similar, CD56 positivity represents a significant diagnostic pitfall. CD56 is useful in distinguishing between granulosa cell tumor and normal ovarian follicles or endometrioid adenocarcinoma. Lack of membranous CD56 expression in fibrothecoma may help differentiate it from granulosa cell tumor. However, CD56 is of limited use for distinguishing between granulosa cell tumor and poorly differentiated carcinoma or endometrial stromal sarcoma. Appropriate and cautious interpretation of CD56 expression should lead to a more accurate diagnosis of granulosa cell tumor.     

A novel human monoclonal antibody against cervical cancer: its immunoreactivity with normal tube and ovary and with ovarian tumor tissue

1-1-2D, a novel human monoclonal antibody (MAb) raised against cervical cancer, was examined for its immunohistochemical reactivity with ovarian cancer. Six of 10 ovarian cancer cell lines showed positive staining, while 3 of 5 cervical cancer cell lines were positive. Among tumor tissues, 15 of 18 (83%) ovarian serous cystadenocarcinomas and 10 of 12 (83%) ovarian clear cell adenocarcinomas were positive. We also performed immunohistochemical staining of the same cancer specimens with OC 125 and compared their reactivity. The frequency of positivity was similar, but the reactivity of the two MAbs was different. 1-1-2D stained the apical surface of the glandular epithelial cells and secretory products of the gland. On the other hand, OC 125 stained the cytoplasm as well as the plasma membrane of the glandular epithelial cells. These results suggest that 1-1-2D MAb recognizes a different antigen from that recognized by OC 125.