恶性上皮性肿瘤角蛋白和波形蛋白的表达

Filed formalin-fixed paraffin blocks of 128 cases of epithelial neoplasms were selected for immunohistochemical study of keratin and vimentin expression. The results showed that 35.1% (45/128) of different carcinomas expressed vimentin. The immuno-positivity of vimentin in thyroid carcinomas, ovarian carcinomas, prostatic adenocarcinomas, pulmonary carcinomas and malignant mesotheliomas were 81.8%, 42.8%, 66.7%, 30.5% and 53.4%, respectively. Carcinomas of breast, kidneys, salivary glands, adrenal glands and nasopharyngeal carcinomas also showed various degrees of positive reaction. The results suggest that an immunohistochemical positive vimentin reaction does not exclude histopathological diagnosis of carcinomas. The significance and noticeable aspects of immunohistochemical methods in histopathological diagnosis are also discussed.     

Endodermal sinus tumor: immunophenotypic expression of a carcinoma.

A series of five endodermal sinus tumors was studied for their cytoskeletal and other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal tumors. The cytoskeletal expression was also studied by gel electrophoresis and immunoblotting. Every tumor was diffusely and strongly immunostained for cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected. Vimentin was focally coexpressed in 4 cases. The stroma was diffusely immunostained for vimentin. None of them expressed desmin, neurofilament, or glial filament protein. Desmoplakin was expressed only in one ovarian tumor. Alpha-fetoprotein and S-100 protein were also diffusely positive among the neoplastic cells; intracytoplasmic globules were especially strongly immunostained. These findings suggest that endodermal sinus tumors represent a group of pure malignant epithelial neoplasms, and may be regarded as primitive carcinomas.     

Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas.

The expression patterns of intermediate filament proteins of primary and metastatic endometrial (n = 18) and ovarian (n = 24) adenocarcinomas were analyzed by immunocytochemistry using a panel of specific antibodies and by gel electrophoresis of cytoskeletal preparations, followed by immunoblotting. All cells of all endometrial adenocarcinomas studied contained the "simple epithelial"-type cytokeratins (CKs) 8, 18, and (mostly) 19, with variable numbers of cells also positive for CK 7 and vimentin. In addition, most of these tumors contained individual cells or groups of cells that were positive for the stratification-related CKs 4, 5, 6, 13, 14, and 17. The latter CKs were often associated with squamous cell foci, but were also found in some single (nonsquamous) tumor cells, indicative of early stages of squamous cell differentiation. Ovarian carcinomas of various histologic types and grades contained predominantly CKs 7, 8, 18, and 19. Serous, endometrioid, and anaplastic tumors, but not mucinous and clear cell tumors, also contained minor amounts of stratification-related CKs in variable combinations, mostly including CK 4. In all tumor types except mucinous tumors, vimentin was consistently detected in variable proportions of tumor cells which, however, were rather low in anaplastic carcinomas. Surprisingly, glial filament protein was detected in a minor proportion (< or = 20%) of tumor cells in seven of 14 serous and endometrioid ovarian carcinomas and in three of 18 endometrial carcinomas. These different intermediate filament expression patterns of müllerian duct-type carcinomas, only partly related to the morphologic appearance of the specific type of tumor, might reflect the multipotentiality of differentiation of müllerian duct-derived epithelia. Cytoskeletal features of potential diagnostic value, especially in metastatic carcinomas, are discussed.     

Keratin and vimentin distribution patterns in the epithelial structures of the cannie anal region

The intermediate filament labeling pattern of the epithelial structures of the canine anal region was studied with different polypeptide specific keratin monoclonal antibodies (MoAbs) and with a monoclonal and polyclonal vimentin antibody. The epithelial structures in this region could be discriminated and characterized by differences in their keratin staining pattern. The basal cells in the different epithelial structures showed a similar staining pattern characterized by reactivity with MoAbs staining keratins 5, 8, 14, and 17. Columnar epithelial cells showed a completely different phenotype mostly characterized by reactivity with MoAbs staining keratins 7, 5, 8, 18, and 19. A restricted number of differentiated perianal gland cells showed perinuclear vimentin staining. Myoepithelial cells did not stain for vimentin, but, as other basal cells, were positive for MoAbs staining keratins 5, 8, 14, and 17.© Willey-Liss, Inc.     

Expression of cytokeratins and vimentin in normal and neoplastic tissue from the bovine female reproductive tract.

The distribution of cytokeratins (CKs) and vimentin in the normal genital tract of calves and cows at different stages of the oestrous cycle and in epithelial tumours of the tract was studied immunohistochemically. Few differences in CK and vimentin immunolabelling were detected in relation to age or stage of the oestrous cycle. Coexpression of CKs in simple epithelia and in basal cells of stratified epithelia was detected in the oviduct and endocervix; this coexpression was different from that previously described in women. The demonstration of CKs but not vimentin in the neoplastic cells of a serous superficial ovarian papilloma suggested an origin from the ovarian surface epithelium, while the coexpression of CKs and vimentin in serous papillary and mucinous cystadenomas pointed to a possible origin from the rete ovarii. Studies on three uterine adenocarcinomas and the ovarian metastases from two of these showed an endometrial-CK phenotype. The intermediate filament profile of normal endometrium, conserved in uterine adenocarcinomas and their ovarian metastases, may be useful in discriminating between ovarian metastases from endometrial carcinomas and those originating from primary carcinomas in other organs.     

Keratin and vimentin distribution patterns in the epithelial structures of the canine anal region.

The intermediate filament labeling pattern of the epithelial structures of the canine anal region was studied with different polypeptide specific keratin monoclonal antibodies (MoAbs) and with a monoclonal and polyclonal vimentin antibody. The epithelial structures in this region could be discriminated and characterized by differences in their keratin staining pattern. The basal cells in the different epithelial structures showed a similar staining pattern characterized by reactivity with MoAbs staining keratins 5, 8, 14, and 17. Columnar epithelial cells showed a completely different phenotype mostly characterized by reactivity with MoAbs staining keratins 7, 5, 8, 18, and 19. A restricted number of differentiated perianal gland cells showed perinuclear vimentin staining. Myoepithelial cells did not stain for vimentin, but, as other basal cells, were positive for MoAbs staining keratins 5, 8, 14, and 17.     

Keratin expression in cervical cancer.

Using a panel of 21 monoclonal and 2 polyclonal keratin antibodies, capable of detecting separately 11 subtypes of their epithelial intermediate filament proteins at the single cell level, we investigated keratin expression in 16 squamous cell carcinomas, 9 adenocarcinomas, and 3 adenosquamous carcinomas of the human uterine cervix. The keratin phenotype of the keratinizing squamous cell carcinoma was found to be most complex comprising keratins 4, 5, 6, 8, 13, 14, 16, 17, 18, 19, and usually keratin 10. The nonkeratinizing variety of the squamous cell carcinoma expressed keratins 6, 14, 17, and 19 in all cases, usually 4, 5, 7, 8, and 18, and sometimes keratins 10, 13, and 16. Adenocarcinomas displayed a less complex keratin expression pattern comprising keratins 7, 8, 17, 18, and 19, while keratin 14 was often present and keratins 4, 5, 10 and 13 were sporadically found in individual cells in a few cases. These keratin phenotypes may be useful in differential diagnostic considerations when distinguishing between keratinizing and nonkeratinizing carcinomas (using keratin 10, 13, and 16 antibodies), and also in the distinction between nonkeratinizing carcinomas and poorly differentiated adenocarcinomas, which do not express keratins 5 and 6. Keratin 17 may also be useful in distinguishing carcinomas of the cervix from those of the colon and also from mesotheliomas. Furthermore the presence of keratin 17 in a CIN I, II, or III lesion may indicate progressive potential while its absence could be indicative of a regressive behavior. Because most carcinomas express keratins 8, 14, 17, 18, and 19, we propose that this expression pattern reflects the origin of cervical cancer from a common progenitor cell, i.e., the endocervical reserve cell that has been shown to express keratins 5, 8, 14, 17, 18, and 19.     

Laminin and type VII collagen distribution in different types of human lung carcinoma: correlation with expression of keratins 14, 16, 17 and 18

The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.     

An immunoperoxidase study of renal cell carcinomas: correlation with nuclear grade, cell type, and histologic pattern

We applied a panel of antibodies to formalin-fixed, paraffin-embedded sections of 55 renal cell carcinomas using a three-stage immunoperoxidase technique. The antibody panel included two anti-keratins, AE1 and CAM5.2, anti-epithelial membrane antigen (EMA), anti-vimentin, anti-S100 protein, and the anti-leukocyte marker PD7/26. Forty-eight of 55 renal cell carcinomas expressed keratins. CAM5.2 stained 46 tumors (84%) and AE1 stained 37 neoplasms (67%). AE1 reacted with two CAM5.2-negative tumors. EMA was expressed by 35 carcinomas (64%), including three of the CAM5.2-negative neoplasms. Therefore, using all three antibodies, 50 neoplasms (91%) expressed antigens of epithelial differentiation. Anti-EMA and AE1 were complementary to each other; the combination stained 46 of the carcinomas, comparable with CAM5.2 alone. Vimentin was expressed by 26 tumors (47%), and S100 was expressed by one. PD7/26 did not stain any of the cases. Vimentin expression correlated with nuclear grade; low nuclear grade neoplasms infrequently expressed vimentin, while the converse was true for high nuclear grade tumors. Keratin expression was related to tumor cell type and histologic pattern, as fewer neoplasms of clear cell type and with a solid pattern expressed keratins. In contrast, all papillary and eight of nine (89%) spindled carcinomas expressed keratins.     

The limited difference between keratin patterns of squamous cell carcinomas and adenocarcinomas is explicable by both cell lineage and state of differentiation of tumour cells.

AIM: To study the differentiation of epithelial tissues within their histological context, and to identify hypothetically, on the basis of keratin pattern, the putative tissue origin of a (metastatic) carcinoma. METHODS: Using well characterised monoclonal antibodies against individual keratins 7, 8, 18, and 19, which are predominantly found in columnar epithelia, and keratins 4, 10, 13, and 14, predominantly expressed in (non)-keratinising squamous epithelia, the keratin patterns for a series of 45 squamous cell carcinomas and 44 adenocarcinomas originating from various epithelial tissues were characterised. RESULTS: The predominant keratins in all adenocarcinomas proved to be 8, 18, and 19. In addition, these keratins were also abundantly present in squamous cell carcinomas of the lung, cervix, and rectum and, to a lesser extent, of the larynx, oesophagus, and tongue, but not in those of the vulva and skin. Keratins 4, 10, 13, and 14 were present in almost all squamous cell carcinomas, but also focally in some of the adenocarcinomas studied. CONCLUSIONS: There is a limited differential expression of distinctive keratin filaments between squamous cell carcinomas and adenocarcinomas. Apparently, squamous cell carcinomas that originate from columnar epithelium by squamous metaplasia gain the keratins of squamous cells but retain the keratins of columnar epithelial cells. However, the simultaneous expression of two of three squamous keratins (4, 10, and 13) identifies a squamous cell carcinoma, and thus might be useful in solving differential diagnostic problems.     

Are keratin proteins a better tumor marker than epithelial membrane antigen? A comparative immunohistochemical study of various paraffin-embedded neoplasms using monoclonal and polyclonal antibodies

Epithelial membrane antigen and keratin proteins represent markers of epithelial differentiation that may be detected in routine formalin-fixed, paraffin-embedded tissues. Eighty-seven neoplasms, including 48 adenocarcinomas of various types, squamous and transitional cell carcinomas, small-cell anaplastic carcinomas, carcinoid tumors, mesotheliomas, hepatomas, melanomas (metastatic), adrenal cortical carcinomas, germ cell tumors, and extramammary Paget's disease, were assessed to determine the relative effectiveness of these antigens as tumor markers. Immunoperoxidase studies were performed using monoclonal antibodies to epithelial membrane antigen and monoclonal (combined AE1 and AE3) and polyclonal (bovine muzzle keratins) antibodies to keratin proteins. In more than half the cases (50/87%), both markers yielded comparable results. However, in 29 cases (33%), keratin proteins were clearly superior to epithelial membrane antigen as a tumor cell marker. Particular discrepancies were apparent for some gastrointestinal adenocarcinomas, squamous cell carcinomas, hepatomas (hepatocellular type), spindle cell components of mesotheliomas, and carcinoid tumors. Epithelial membrane antigen represented a better marker in eight cases (9%), mainly for small-cell anaplastic carcinomas and some renal cell and pulmonary adenocarcinomas. Adrenal cortical carcinomas, melanomas, and seminomas were nonimmunoreactive for both antigens. Epithelial membrane antigen and keratin proteins represent useful complementary markers in diagnostic surgical pathology.     

Immunohistochemistry of ovarian granulosa cell tumours

Summary Paraffin-embedded material of 47 ovarian tumours primarily diagnosed as granulosa cell tumours, including 2 cases of juvenile granulosa cell tumour, were studied immunohistochemically for the presence of intermediate filament proteins, epithelial membrane antigen and tumour markers. Forty-one lesions, including the 2 juvenile granulosa cell tumours, were vimentin positive, while keratin and epithelial membrane antigen expression could not be detected. Six tumours primarily diagnosed as poorly differentiated malignant granulosa cell tumours were vimentin negative, showed a mild to moderate positivity for keratin and intense positivity with the anti-epithelial membrane antigen antibody. These latter tumours were therefore classified as undifferentiated ovarian carcinomas, corresponding to their significantly poorer prognosis and shorter survival when compared with the granulosa cell tumours. Two of these six tumours were positive for carcino-embryonic antigen. Two small cell carcinomas of the ovary studied in addition expressed keratin in a proportion of tumour cells while no epithelial membrane antigen or vimentin was detectable. None of the tumours tested for alpha-fetoprotein, human chorionic gonadotrophin, human placental alkaline phosphatase and human placental lactogen, were positive.The data indicate the value of antibodies directed against intermediate filament proteins and epithelial membrane antigen to distinguish granulosa cell tumours from poorly differentiated carcinomas, a worthwhile distinction considering the much better prognosis of granulosa cell tumours.     

Changes in expression of differentiation markers between normal ovarian cells and derived tumors.

The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors.     

Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction.

Vimentin expression, growth fractions (GF), and estrogen receptor (ER) levels were determined for 90 untreated primary breast carcinomas. Coexpression of keratin and vimentin was found in approximately 20% of the tumors regardless of menopausal status. Vimentin was expressed preferentially in tumor cells of high-grade ductal breast carcinomas (15 of 28 histologic grade 3 vs. 0 of 40 grades 1 and 2). Vimentin expression was found preferentially in tumors with high GF (greater than 15% Ki-67 positive by immunoperoxidase staining) and low ER levels (less than 60 fmols/mg protein by a monoclonal enzyme immunoassay). Sixty-eight percent of tumors in this group were vimentin positive and 88% of all vimentin-positive tumors fell into this category. More than 50% of the tumor cells coexpressed vimentin and keratin. Thus, vimentin expression may be helpful in identifying a substantial subset of ER-independent breast carcinomas with poor prognostic indicators.     

Expression of keratins 1, 6, 15, 16, and 20 in normal cervical epithelium, squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma.

Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition.     

Marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas.

To investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies, a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as granulosa cell tumor. Using monoclonal antibodies against different keratin subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4 and 13 were not found in mesothelial cells, but positive groups of cells were identified in several cystomas, adenomas, and carcinomas. While mesothelial cells did not react with the pan-epithelial marker BW495/36, invaginating metaplastic mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an increasing reactivity with BW495/36, with an increasing degree of malignancy. The reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC 125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50% of the ovarian cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or disappeared in granulosa cells of mature follicles (Graafian follicles), whereas granulosa cell tumors did not react with anti-keratin antibodies. The reactivity of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian carcinoma-associated antigens were not expressed in granulosa cells or granulosa cell tumors. The data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production of ovarian carcinoma associated antigens, in addition to focal production of keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200-kd glycoprotein and the ovarian carcinoma-associated antigens.     

The expression of keratins Nos. 8, 17 and vimentin in pleomorphic adenoma of the salivary glands

In the normal salivary gland, the monoclonal antibody to keratin 8 immuno-morphologically identifies the epithelium that covers acini and ducts. The monoclonal antibodies to keratin 17 and vimentin detect normal myoepithelium. The two keratins are found both in the epithelioid and mesenchyma-like components of pleomorphic adenoma, suggesting a single epithelial nature of this tumor. In all the morphological components of the pleomorphic adenoma, there are cells that combine protein expression of intermediate filaments normally labelling different cell subpopulations. This fact provides support for the hypothesis that the pleomorphic adenoma originates from bipotent precursor cells. A particular phenotype of pleomorphic adenoma elements is realized under the control of the local density of cells and microenvironment, as a result of which the cells expressing vimentin predominate in the mesenchymal component, keratin 8 in the epithelial tubular one.     

Expression of intermediate filament proteins in thyroid gland and thyroid tumors

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.     

VIMENTIN EXPRESSION IN CERVICAL CARCINOMAS: ASSOCIATION WITH INVASIVE AND MIGRATORY POTENTIAL

Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Vimentin expression has previously been associated with invasive properties in an in vitro model consisting of a set of HPV-33-transformed cervical keratinocyte cell lines.^1,2 In the present study, in order to emphasize those in vitro findings, the expression of vimentin has been investigated in cervical neoplasms of different grades, using immunohistochemistry. A clear association is reported between vimentin expression and metastatic progression, since vimentin was detected in all invasive carcinomas and lymph node metastases, but not in CIN III lesions. These in vivo results are compared with present and previous data obtained in vitro on cervical keratinocyte cell lines, where vimentin expression also correlated with in vitro invasiveness.     

Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects.

Five monoclonal antibodies recognizing different keratin polypeptides in immunoblotting or different epithelial cell types in complex tissues were studied for their suitability as reagents for the differential diagnosis of primary and secondary malignant epithelial liver tumors. The broad specificity keratin antibodies lu-5 and KL-1 stained all epithelial liver neoplasms. In contrast the antibodies CK-7 (Ker-7-specific), CK-2 (Ker-18-specific) and KA-4 (Ker-19-specific in liver) allow these neoplasms to be divided into three groups: Hepatocellular carcinomas were CK-2-positive and CK-7-negative. Cholangiocellular carcinomas, liver metastases of extrahepatic bile duct carcinomas, liver metastases of a ductal carcinoma of breast, and a follicular thyroid carcinoma were stained positively by CK-2, CK-7, and KA-4. In 1 of 6 hepatocellular carcinomas neoplastic hepatocytes were focally labeled by KA-4. In a focal nodular hyperplasia of the liver modified hepatocytes were decorated not only by CK-2 but also by CK-7 and KA-4. Liver metastases of colorectal adenocarcinomas and of a carcinoid tumor were stained positively by CK-2 and KA-4 but not by CK-7.