Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas.

Monoclonal antibodies (MAbs) to specific keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to keratin 7 (RCK 105, OV-TL 12/30) and keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The keratin 18 MAbs distinguished adenocarcinomas (which are keratin 18 positive) from most squamous cell carcinomas (which are generally keratin 18 negative). The MAbs to keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (keratin 7 positive) and carcinomas of the gastrointestinal tract (keratin 7 negative), or between transitional cell carcinomas (keratin 7 positive) and prostate cancer (keratin 7 negative). In general, malignancies showed the expected keratin reactivity pattern as concluded from the keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same keratin protein were observed, both in the normal and malignant human tissues, indicating that specific keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and cytopathology, in which they add to a more refined diagnosis of (adeno)carcinomas.     

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.     

A novel monoclonal antibody to cytokeratin 18 with reactivity toward lung squamous cell carcinomas and adenocarcinomas of various sites.

Antibodies to cytokeratins (CKs) have found extensive application in the differential diagnosis of epithelial tumors. The chain-specific anti-CK reagents appear to be of practical value for further subtyping of carcinomas. The authors have produced a novel anti-CK 18 monoclonal antibody (ACK-156) using a modified immunization procedure that included sequential injections of human epidermal keratin, cyclophosphamide, and enriched cytoskeletal extracts from a human lung carcinoma cell line. This protocol effectively amplified clones with reactivity toward CK epitopes not present in epidermal keratin. Monospecificity of the antibody was confirmed by immunoblot analysis using both total cell lysates and cytoskeletal extracts as antigens. Immunoperoxidase staining of adenocarcinomas from a variety of sites, including lung, was strongly positive. Squamous cell carcinomas of lung were also strongly stained whereas squamous cell carcinomas of head and neck origin were stained focally or not at all. In contrast, several commercially available anti-CK 18 monoclonal antibodies did not distinguish squamous cell carcinomas of lung from those of head and neck origin. Immunoblot analysis of tumor lysates corroborated the tissue staining results and revealed that the commercially available antibodies that were tested recognize at least one other low molecular weight peptide in addition to the CK 18 peptide recognized by ACK-156.     

Pathogenesis and histomorphology of ampullary carcinomas and their precursor lesions. Review and individual findings

Most adenomas and carcinomas of small intestine and extrahepatic bile ducts arise in the region of Vater's papilla. In FAP it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis in an early tumor stage. In about 80% curative intended resection is possible. Operability is the most relevant prognostic factor. Inflammatory changes, fibrosis, regeneratory changes after endoscopic manipulation, hyperplasia, preneoplastic lesions close to carcinoma, deeply sited carcinomas under protruded, non-neoplastic duodenal mucosa make the diagnosis difficult on biopsy material. Histologically, intestinal type adenocarcinoma, pancreatobiliary type adenocarcinoma, undifferentiated carcinomas and unusual types can be differentiated. In our own series comprising 45 resected ampullary carcinomas 6 from 10 intestinal type adenocarcinomas, and 4 carcinomas of unusual types expressed the immunohistochemical marker profile of intestinal mucosa (keratin 7-, keratin 20+, MUC2+). 17 from 21 pancreatobiliary type adenocarcinomas, 4 undifferentiated carcinomas, as well as 3 papillary carcinomas showed the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20-, MUC2-). 3 invasive carcinomas which were negative for these markers, showed one of these characteristic marker-combinations in non-invasive adenomatous parts. These findings support the concept of histogenetically different ampullary carcinomas which are developing from the intestinal or from the pancreaticobiliary type mucosa of Vater's papilla. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear in different frequencies. In future studies molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. The histologic classification should reflect consequently the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Cytokeratins of normal epithelia and some neoplasms of the female genital tract

Cytokeratins are a family of polypeptides of intermediate filaments which in diverse epithelia are expressed in different, yet specific, combinations. We have studied the cytokeratins present in normal epithelia of the female genital tract, in comparison with those present in genital tract carcinomas, by two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues and by immunofluorescence microscopy. Cells of ovarian mesothelium, oviduct, endometrium, and endocervix contain cytokeratin polypeptides nos. 7, 8, 18, and 19. By contrast, tonofilaments of the stratified squamous epithelia of vagina and exocervix contain cytokeratins 4, 5, 6, 13, 14, 15, 16, and 19. Exocervical regions distant from the endo-exocervical junction as well as vagina contain, in addition, the large (Mr 68,000) and basic cytokeratin component no. 1, previously described in epidermis. Endocervical squamous metaplasia at the endo-exocervical border displays a complex cytokeratin pattern, probably due to cell-type heterogeneity. Similar cytokeratin patterns are also observed in genital tract epithelia of the cow and mouse. In human carcinomas of the female genital tract, two main types of cytokeratin patterns can be distinguished. Ovarian carcinomas and endometrial adenocarcinomas express cytokeratins 7, 8, 18, and 19 and, thus, maintain the pattern of the cells of their origin. In endocervical adenocarcinomas the additional presence of component no. 17 has been noted. Nonkeratinizing squamous cell carcinomas of the cervix show a very complex pattern (cytokeratins 5, 6, 7, 8, 13, 14, 15, 17, 18, and 19). Keratinizing squamous cell carcinomas of the cervix display lower complexity and lack cytokeratins 7, 8, and 18. When frozen sections are examined by immunofluorescence microscopy, all epithelia of the genital tract are stained with the monoclonal cytokeratin antibody KG 8.13. Simple epithelia but not the stratified epithelia of vagina and exocervix also react with monoclonal antibodies specific for cytokeratins 8 or 18. The value of cytokeratin polypeptide patterns in distinguishing diverse epithelial cell types of the female genital tract, in elucidating the histogenesis of neoplasms, and in providing a new tool for the differential diagnosis of tumors is discussed.     

Immunoreactivity for epithelial and neuroendocrine antibodies are useful in the differential diagnosis of lung carcinomas

The histologic classification of pulmonary neoplasms can have important implications regarding appropriate management of patients. Although the histologic classification of lung tumors is predominantly based on morphology, ancillary studies such as immunohistochemistry can be used in difficult cases, and the diagnosis of large cell neuroendocrine carcinoma requires confirmation of neuroendocrine differentiation by immunohistochemistry or electron microscopy. We immunostained 142 lung tumors for B72.3, keratin 34betaE12, keratin 7, keratin 14, keratin 17, synaptophysin, and chromogranin to determine the utility of neuroendocrine markers and epithelial markers in the differential diagnosis. Among neuroendocrine carcinomas (small cell carcinoma and large cell neuroendocrine carcinoma), 84% (37 of 44) were chromogranin positive, 64% (21 of 36 small cell, 6 of 6 large cell neuroendocrine) were synaptophysin positive, 5% (2 of 43) were keratin 34betaE12 positive, 9% (4 of 44) were keratin 7 positive, and 5% (2 of 37) of small cell carcinomas and 50% (3 of 6) of large cell neuroendocrine carcinomas were B72.3 positive. Among non-neuroendocrine carcinomas, 5% (5 of 98) were chromogranin positive, 3% (3 of 96) were synaptophysin positive, and 97% (95 of 98) were positive for either keratin 34betaE12 or keratin 7 and 99% (97 of 98) were positive for either keratin 34betaE12, keratin 7 or B72.3. An antibody panel consisting of keratin 7, keratin 34betaE12, chromogranin, and synaptophysin separated 132 of 141 tumors (94%) into distinct groups. We conclude that immunostaining with both neuroendocrine markers and epithelial markers can be useful in the differential diagnosis of lung neoplasms.     

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.     

Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hales colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.     

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.     

Stereology, flow cytometry, and immunohistochemistry of follicular neoplasms of the thyroid gland

A retrospective analysis of surgically resected thyroid cold solitary nodules was performed by stereology, DNA flow cytometry, and immunohistochemistry in 15 follicular adenomas and 15 well-differentiated follicular carcinomas to determine if a differential diagnosis of both follicular neoplasms can be done exclusively from cytologic criteria. Between 150 and 200 tumor cell nuclei (TCN) were studied per case for their TCN profile area, perimeter, and density, as well as for stereologic estimates, including the new parameter, volume-weighted mean particle volume (Vv). Flow-cytometric analyses included measurement of the DNA index and the percentage of cells in S phase and G2M phase. The same tumors were examined for the expression of thyroglobulin and the intermediate filaments vimentin and keratin. Follicular adenomas and follicular carcinomas did not show any significant differences in stereologic estimates related to TCN size. Both groups included similar proportions of diploid and aneuploid neoplasms. Aneuploid follicular neoplasms showed a significantly greater area, perimeter, and volume of TCN as compared with diploid tumors, regardless of their histologic diagnosis. Follicular adenomas and follicular carcinomas expressed a similar staining pattern for the tested immunoreagents, with a few cases coexpressing vimentin and keratin. From our results, a differential diagnosis of follicular neoplasms cannot be performed on the basis of cytologic aspirates exclusively. Infiltration of capsula or vessels remains the only safe indicator of malignancy in the absence of metastases. The lack of cytologic differences suggests that some follicular adenomas are preinvasive carcinomas, not yet showing infiltrative growth at the time of resection.     

Expression of keratin 19 distinguishes papillary thyroid carcinoma from follicular carcinomas and follicular thyroid adenoma

Keratin expression with the use of chain-specific monoclonal antikeratin antibodies was investigated in normal thyroid tissue (n = 4), colloid nodules (n = 19), follicular thyroid adenomas (n = 18), follicular carcinomas (n = 10), and papillary carcinomas (n = 12). Frozen sections were stained with monoclonal antibodies M20 (keratin 8), M9 (keratin 18), and LP2K (keratin 19) with the use of the indirect immunoperoxidase technique. The immunohistochemical findings showed that the expression of keratins 8 and 18 was equally extensive in all normal, benign, and malignant lesions tested. In contrast, different staining patterns were observed with the use of monoclonal antibody to keratin 19. Follicular carcinomas were only focally stained with this antibody or were not reactive at all. Keratin 19, however, was present in all the tumor cells of papillary tissues and in a moderate amount of cells of nonneoplastic thyroid lesions and follicular adenomas. In papillary carcinoma, an identical homogeneous expression of keratin 19 was observed in both papillary and follicular structures, which suggests a common cellular origin. These results show that immunohistochemical staining with the use of monoclonal antibody against keratin 19 is useful to distinguish papillary thyroid carcinomas from follicular adenomas and follicular thyroid carcinomas.     

Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of nonalcoholic fatty liver disease. Definitive histologic identification of ballooned hepatocytes on routine stains, however, can be difficult. Immunohistochemical evidence for loss of the normal hepatocytic keratin 8/18 can serve as an objective marker of ballooned hepatocytes. We sought to explore the utility of a keratin 8/18 plus ubiquitin double immunohistochemical stain for the histologic evaluation of adult nonalcoholic fatty liver disease. Double immunohistochemical staining for keratin 8/18 and ubiquitin was analyzed using 40 adult human nonalcoholic fatty liver disease core liver biopsies. Ballooned hepatocytes lack keratin 8/18 staining as previously shown by others, but normal-size hepatocytes with keratin loss are approximately 5 times greater in number than keratin-negative ballooned hepatocytes. Keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin deposits show a zonal distribution, are positively associated with each other, and are frequently found adjacent to or intermixed with fibrous matrix. All 3 lesions correlate with fibrosis stage and the hematoxylin and eosin diagnosis of steatohepatitis (all P < .05). Compared with hematoxylin and eosin staining, immunohistochemical staining improves the receiver operating characteristics curve for advanced fibrosis (0.77 versus 0.83, 0.89, and 0.89 for keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin, respectively) because immunohistochemistry is more sensitive and specific for fibrogenic hepatocellular injury than hematoxylin and eosin staining. Keratin 8/18 plus ubiquitin double immunohistochemical stain improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Thus, it may help differentiate nonalcoholic steatohepatitis from nonalcoholic fatty liver.     

Mapping of the keratin polypeptides in meningiomas of different types: an immunohistochemical analysis of 463 cases

Keratins are known to be expressed in some meningiomas, and they have been consistently reported in secretory meningiomas. However, the expression of individual keratin polypeptides has not yet been systematically explored, and such a study could provide important information for the differential diagnosis of meningioma and other tumors, particularly metastatic carcinomas. In this study we analyzed the keratin polypeptide patterns of 463 meningiomas of different types using well-characterized monoclonal antibodies specific to 11 individual keratins and 3 additional antibodies that recognize more than 1 keratin. Archnoid tissues from autopsies were examined for comparison. Secretory meningiomas showed consistent positivity for all simple epithelial keratins K7, K8, K18, and K19, usually limited to the slender spindle cells lining the gland-like lumina. Other keratins variably detected in a minority of gland-like structures were K5/6, K14, K16, and K17. Among other meningiomas, keratin 18 was commonly present in a significant number of tumor cells in different subtypes (30% to 80% of cases), often extensively. The K18 positivity of meningiomas paralleled that observed in normal arachnoids, which were negative for K7, K8, K19, and AE1. Only rare meningiomas, other than the secretory ones, had significant positivity for K7, K8, K19, and other keratins than K18. The concentric spindle cells around psammoma bodies and few other spindle cell foci were often focally positive for K7 and to lesser degree for K8, K14, and K19. The complex pattern of keratins in meningiomas has to be considered in the differential diagnosis of meningioma and metastatic carcinoma. In this context, antibodies to K7, K8, and K19 and the antibodies AE1 and AE3 are useful, because they only rarely label significant numbers of meningioma cells but are positive in a great majority of carcinomas. Careful histologic analysis is necessary to differentiate anaplastic meningiomas and metastatic carcinomas, which have overlapping patterns of several keratins except K20, which was never present in any type of meningioma.     

胃肠道癌单克隆抗体在鉴别原发性与转移性卵巢癌中的意义

Monoclonal antibodies MG7 and MC3, which are highly specific for gastrocolonic carcinomas, were used in immunohistochemical studies of detecting the relevant antigens present in the primary and metastatic carcinomas in ovaries. All 33 cases of primary ovarian carcinomas examined were negative, and positive reaction was obtained in 94.4% of 18 cases of metastatic carcinomas in ovaries. Results of this investigation confirmed the specificity of MG7 and MC3 in differential diagnosis of primary ovarian cancers from metastatic cancers in ovaries originating from the gastrointestinal tract.     

Immunoperoxidase staining of malignant cells in pleural effusions

The indirect immunoperoxidase method was used to detect the presence of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), keratin and alpha-1-antichymotrypsin (alpha 1ACT) in cells of pleural fluid sediments from 30 patients with pleural malignancies (18 mesotheliomas and 12 metastatic carcinomas). CEA was negative in all mesotheliomas and positive in all carcinomas but one (an ovarian serous cystadenocarcinoma); alpha 1ACT was positive in mesotheliomas and negative in carcinomas; EMA and keratin were positive in both types of tumor. These data suggest that the use of immunostaining against CEA and alpha 1ACT seems to improve the cytologic differential diagnosis between malignant mesothelioma and metastatic carcinoma in pleural effusions.     

OV-TL 12/30 (keratin 7 antibody) is a marker of glandular differentiation in lung cancer

The immunoreactivity of OV-TL 12/30, a monoclonal antibody to keratin 7 was investigated on paraffin-embedded human lung cancer tissues of 61 patients. A modified AEC-immunoperoxidase method with pepsin pre-digestion was used. In normal lung tissue keratin 7 was found in bronchial and bronchiolar epithelium, pneumocytes and compound glands. Squamous metaplasia of the bronchial tree was negative. All 24 squamous cell carcinomas were negative irrespective of grade of differentiation. All differentiation grades of 20 adenocarcinomas including bronchioalveolar carcinomas were positive. Since six large cell anaplastic carcinomas did not react with keratin 7 antibody these tumours are considered to be of squamous cell rather than adenocarcinomatous origin. Small cell anaplastic carcinomas were negative in 10 of 11 cases. Our study demonstrates that this keratin 7 antibody is useful in differentiating between squamous cell carcinoma and adenocarcinoma of the lung and it may be particularly useful in making the correct diagnosis in small lung biopsy specimens.     

Immunologic marker analysis of normal and malignant histiocytes. A comparative study of monoclonal antibodies for diagnostic purposes

The authors investigated the phenotype of "monocyte-derived histiocytes/macrophages" on frozen sections of various human tissues, in 12 histiocytic tumors, and in 15 large cell non-Hodgkin's lymphomas. The monoclonal antibodies (MAbs) considered specifically directed against antigens associated with monocytes/histiocytes included the following: Leu-M1, Leu-M3, Leu-M5, My4, My7, My8, My9, anti-Monocyte 1, anti-Monocyte 2, RFD-7, RFD-9, OKM1, and FMC17. The histiocytes in normal tissues and the tumor cells of the histiocytic malignancies expressed these antigens in various degrees. They were not reactive with MAbs specific for lymphocytes, myeloid cells, or Reed-Sternberg cells (Ki-1 antigen). Out of these 13 MAbs, only the labeling by MAb Leu-M3, Leu-M5, anti-Monocyte 1, and RFD-7 was restricted to normal and malignant monocytes/histiocytes. In combination with their broad labeling of different types of monocytes/macrophages, these MAbs are of value in differential diagnostic purposes to distinguish histiocytic malignancies from large cell lymphomas. However, none of the 13 MAbs can be considered as pan-histiocytic reagents because they did not recognize all cell types belonging to the mononuclear/phagocytic system.     

Immunocytochemical criteria in the differential diagnosis of malignant melanoma versus carcinoma, lymphoma and sarcoma in fine needle aspirates.

Monoclonal antibodies to keratin, vimentin, leukocyte common antigen (LCA) and S-100 protein have been used in fine needle aspirates of 35 metastatic malignant melanomas, 136 carcinomas, 35 sarcomas and 82 non-Hodgkin's lymphomas in search for immunocytochemical criteria useful in differential diagnosis of melanoma versus carcinoma, non-Hodgkin's lymphoma and sarcoma. All melanomas expressed vimentin and did not express keratin. Six of 14 melanomas contained S-100 protein. All carcinomas were keratin positive. Some were also vimentin positive. All sarcomas expressed vimentin. Synovial sarcomas were also keratin positive. All NHLs were vimentin positive, keratin negative. All NHLs except one expressed also LCA. It is concluded that keratin, vimentin and LCA are useful markers in differential diagnosis of malignant melanoma versus carcinoma and non-Hodgkin's lymphoma in fine needle aspirates when used together with morphologic and clinical data. However, in differential diagnosis of malignant melanoma and sarcoma these markers are of little use.