Variability of Expression and Arrangement of Cytokeratin and Neurofilaments in Cutaneous Neuroendocrine Carcinomas (Merkel Cell Tumors): Immunocytochemical and Biochemical Analysis of Twelve Cases

Twelve specimens of cutaneous neuroendocrine carcinomas (Merkel cell tumors) available as fresh tissue were analyzed for intermediate filament (IF) expression by immunocytochemical and biochemical methods. In immunofluorescence microscopy, most cases were positive for both simple-epithelium-type cytokeratins and the neurofilament L-and M-polypeptides. Several different IF staining patterns ranging from presence of plaque-like structures (fibrous bodies) only to nearly exclusive expression of delicate cytokeratin fibrils could be distinguished. In immunoelectron microscopy the labeling for both cytokeratin and neurofilament polypeptides seemed evenly distributed among the IFs of the fibrous bodies. In primary culture, tumor cells maintained the coexpression of both IF types. Desmoplakin-positive true desmosomes were found in 5 specimens. Biochemically, cytokeratins nos. 8, 18 and, variably, 19, as well as IT protein and, in many specimens, the neurofilament L-protein and a putative neurofilament M-protein were detected. Only traces of the neurofilament H-polypeptide were found. Our results show that a coexpression of cytokeratin IFs and neurofilaments in variable patterns is a characteristic feature of cutaneous neoendocrine carcinomas; occasionally, however, neurofilaments may be very scarce. The biological, histogenetic and diagnostic implications are discussed.     

Variability of Expression and Arrangement of Cytokeratin and Neurofilaments in Cutaneous Neuroendocrine Carcinomas (Merkel Cell Tumors): Immunocytochemical and Biochemical Analysis of Twelve Cases

Twelve specimens of cutaneous neuroendocrine carcinomas (Merkel cell tumors) available as fresh tissue were analyzed for intermediate filament (IF) expression by immunocytochemical and biochemical methods. In immunofluorescence microscopy, most cases were positive for both simple-epithelium-type cytokeratins and the neurofilament L-and M-polypeptides. Several different IF staining patterns ranging from presence of plaque-like structures (fibrous bodies) only to nearly exclusive expression of delicate cytokeratin fibrils could be distinguished. In immunoelectron microscopy the labeling for both cytokeratin and neurofilament polypeptides seemed evenly distributed among the IFs of the fibrous bodies. In primary culture, tumor cells maintained the coexpression of both IF types. Desmoplakin-positive true desmosomes were found in 5 specimens. Biochemically, cytokeratins nos. 8, 18 and, variably, 19, as well as IT protein and, in many specimens, the neurofilament L-protein and a putative neurofilament M-protein were detected. Only traces of the neurofilament H-polypeptide were found. Our results show that a coexpression of cytokeratin IFs and neurofilaments in variable patterns is a characteristic feature of cutaneous neoendocrine carcinomas; occasionally, however, neurofilaments may be very scarce. The biological, histogenetic and diagnostic implications are discussed.     

An analysis of the sensitivity and specificity of the cytokeratin marker CAM 5.2 for epithelial tumours. Results of a study of 203 sarcomas, 50 carcinomas and 28 malignant melanomas

Two hundred and three sarcomas, 40 carcinomas, 10 carcinomas with spindle cell features, 27 malignant melanomas and one spindle cell melanoma were examined using CAM 5.2, a monoclonal antibody to cytokeratin. This antibody which was prepared against colorectal carcinoma cells and which identifies low molecular weight intermediate filament cytokeratin proteins is suitable for use in formalin fixed, paraffin embedded material. Seventeen of the 203 sarcomas showed positive staining. These included 15/21 synovial sarcomas, 1/5 epithelioid sarcomas and 1/18 malignant neural tumours. Five carcinosarcomas showed positive staining of their epithelial components but negative staining of their spindle cell components; three out of four pure spindle cell carcinomas stained positively; a metastasis from a spindle cell renal carcinoma was negative. A spindle cell thymoma also stained positively. Thirty-seven of the 40 carcinomas stained positively; the three negative carcinomas were a squamous cell carcinoma, a renal cell carcinoma and an oat cell carcinoma. All malignant melanomas were negative. These results are compared with those of other workers and the sensitivity and specificity of CAM 5.2 as an epithelial marker is assessed.     

Neuroendocrine differentiation in adrenocortical carcinoma. New immunohistochemical findings supported by electron microscopy.

Ten adrenocortical carcinomas including two tumors with clinically detectable corticosteroid production, were immunohistochemically analyzed for their intermediate filament proteins, and for neuroendocrine markers. Keratins were present in 6 of 10, vimentin in all 10, and the 68 kilodalton kD neurofilament subunit protein in 6/10 tumors. Keratins numbers 8 and 18 were most prevalent, whereas only traces of keratins 19 and 7 were found. Eight tumors were positive for synaptophysin at least focally, and 3 showed extensive positivity in more than 30% of tumor cells. The tumors showed approximately similar levels of neuron-specific enolase (NSE) expression as judged by immunohistochemistry. Chromogranin was not detected, and there was no immunoreactivity for 3 neuropeptides (calcitonin, gastrin, somatostatin). In normal adrenal cortex, neuron-specific enolase, synaptophysin and neurofilaments were restricted to the nerves seen between the cortical cells. Electron microscopy revealed clusters of dense-core granules in 4 of 5 tumors, consistent with neuroendocrine granules. These results indicate that adrenocortical carcinomas may show signs of neuroendocrine differentiation and share some features with the adrenal medullary tumors.     

Immunohistochemical examination of 25 cases of Merkel cell carcinoma: a comparison with small cell carcinoma of the lung and oesophagus, and a review of the literature.

Merkel cell carcinomas (MCC) were compared to small cell carcinomas of the lung (SCCL) and oesophagus (SCCO). Most MCC were of the intermediate cell type while SCCL and SCCO were usually of the small cell type. Only MCC of trabecular type could be separated from SCCL and SCCO by means of histopathological examination alone. All MCC (25) stained with cytokeratin CAM 5.2, 20 of which in a "paranuclear globular" or combined "paranuclear globular"/diffuse pattern while 17 MCC stained with cytokeratin AE1/AE3. Cytokeratin CAM 5.2 reacted with 60 percent of the SCCL and 86 percent of the SCCO, and cytokeratin AE1/AE3 with 33 and 28 percent respectively. Neurofilament stained 17 MCC in a "paranuclear globular" pattern but none of the SCCL and SCCO. All MCC with a diffuse staining pattern for cytokeratin CAM 5.2 were negative for neurofilament. The results of this study and review of the literature indicate that in most instances Merkel cell carcinoma can be separated from other SCC, pulmonary as well as extrapulmonary, by means of histopathological and, above all, immunohistochemical examinations.     

Coexpression of intermediate filaments in squamous cell carcinomas of upper aerodigestive tract before and after radiation and chemotherapy

Frozen sections of 48 squamous cell carcinomas and seven undifferentiated carcinomas of the upper aerodigestive tract were investigated immunohistochemically with monoclonal antibodies specific for keratin, vimentin, desmin, neurofilaments, and glial fibrillary acidic proteins. In nine squamous cell carcinomas (19%) and six undifferentiated carcinomas (86%) obtained before treatment coexpression of keratin and vimentin was detected in some tumor cells by double immunofluorescence studies. Nine squamous cell carcinomas expressed neurofilaments in scattered tumor cells. Coexpression of vimentin or neurofilaments was seen especially in the peripheral cell layer of the tumor nests and did not seem to correlate with the degree of differentiation. Three undifferentiated carcinomas additionally expressed desmin, and one tumor contained neurofilaments. Glial fibrillary acidic proteins were not detected. Increased coexpression of keratin with vimentin, desmin, or neurofilaments was seen in some tumors that were studied before and after radiation/chemotherapy, suggesting that the intermediate filament profile of tumor cells can be altered by external influences.     

Neuroendocrine skin carcinoma coexpressing cytokeratin and neurofilament proteins

Neuroendocrine (Merkel cell) carcinomas of the skin have been recognized as such for several years. Given the reported wide variability in the morphology and clinical evolution of these tumors, the notion that may they comprise several variants rather than a single type has been advocated. Electron microscopy has played a key role in the early recognition of these tumors while immunohistochemical studies for various neuroendocrine markers have facilitated their subsequent diagnosis and improved our understanding as to their complexity by the demonstration of immunoreactivity for NSE (neuron specific enolase) and a number of neuropeptides. There has also been considerable interest in the study of the cytoskeletal intermediate filament complement of neuroendocrine neoplasms in general and of those of the skin in particular. Early reports indicated that neuroendocrine skin carcinomas had neurofilaments while subsequent investigations determined that they had cytokeratin. However, more recent studies have indicated that at least some neuroendocrine skin carcinomas could in fact coexpress both aforementioned classes of intermediate filament proteins. This brief report is presented to confirm the latter investigations.     

Small cell carcinoma of urinary bladder is differentiated from urothelial carcinoma by chromogranin expression, absence of CD44 variant 6 expression, a unique pattern of cytokeratin expression, and more intense γ-enolase expression

AIMS: Small cell (neuroendocrine) carcinoma of the urinary bladder is clinically more aggressive than urothelial (transitional cell) carcinoma. We have investigated the immunohistochemical markers most useful in diagnosing small cell carcinoma in bladder. METHODS AND RESULTS: We evaluated the expression of chromogranin A, CD44 variant 6 (CD44v6), cytokeratin (CAM 5.2), gamma-enolase, synaptophysin, and CD45 in 46 small cell carcinomas of the bladder. Small cell and urothelial carcinoma were mixed in 21 (46%) cases. The two immunohistochemical markers with best ability to discriminate between small cell and urothelial carcinoma were chromogranin A and CD44v6. Chromogranin A had 97% specificity for small cell carcinoma, staining 65% of cases with 2+/3+ mean intensity; only one case (5%) of urothelial carcinoma was weakly (1+/3+) positive. CD44v6 was 80% specific for urothelial carcinoma, with immunoreactivity in 60% of cases, compared with 7% of small cell carcinoma cases. In cases positive for CD44v6, the mean percentage of reactive urothelial carcinoma cells was 75% (range 10-100%), greater than the 12% of cells in three cases of small cell carcinoma (P = 0.31); further, the pattern of immunoreactivity was membranous vs. focal cytoplasmic, respectively. All small cell carcinomas stained with one of the three neuroendocrine markers tested; 76% of cases were reactive for synaptophysin and 93% for gamma-enolase, with specificities of 86% and 73% in comparison to urothelial carcinoma. gamma-enolase staining of small cell carcinoma was more intense (P = 0.01) than for urothelial carcinoma. Cytokeratin CAM 5.2 stained a mean 47% of cells in small cell carcinoma, always in a punctate perinuclear pattern, and 75% in urothelial carcinoma, in a membranous pattern. CONCLUSIONS: CD44v6, chromogranin A, and possibly gamma-enolase and cytokeratin (CAM 5.2) help differentiate small cell carcinoma from urothelial carcinoma.     

Large cell neuroendocrine carcinoma of the thymus

 

Aim:

We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus.  

Case details:

A 68-year-old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later. Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high-power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron-specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot-like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma.  

Conclusions:

Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.     

Immunohistochemical assessment of proliferative activity in mammary adenomyoepithelioma

Aims : Two cases of adenomyoepithelioma of the breast were examined by immunohistochemistry to evaluate proliferative activity of epithelial and myoepithelial components. Methods and results : The tumours showed a bicellular pattern of gland-forming epithelial cells and proliferative myoepithelial cells with clear cytoplasm. They showed foci of monotonous growth of myoepithelial cells devoid of glands with low mitotic rate (1 ∼ 2/10 high-power fields) and mild cytological atypia. Immunohistochemically, the glandular cells were positive for epithelial membrane antigen, cytokeratin (KL-1 and CAM5.2) and carcinoembryonic antigen, whereas tumour cells with clear cytoplasm were reactive with muscle-specific actin (MSA), alpha smooth muscle actin, vimentin, and S100 protein but negative for desmin. Proliferative activities assessed by MIB-1(Ki-67)/MSA positive cell index were greater in myoepithelial cells in both cases (19.2% and 17.7%) as compared to those in epithelial cells (MIB-1/CAM5.2 index: 10.2% and 9.5%). Conclusions : These results might account for the previous findings that myoepithelial components predominate over the epithelial ones in an advanced stage of this tumour as well as in recurrent or metastatic lesions.     

Vimentin expression of renal cell carcinoma in relation to DNA content and histological grading: a combined light microscopic, immunocytochemical and cytophotometrical analysis

An immunocytochemical and cytophotometrical analysis of 30 renal cell carcinomas was carried out in order to investigate the expression of cytokeratin and vimentin in relation to the ploidy and mitotic index. Thirty renal cell carcinomas were studied using monoclonal antibodies CAM 5.2 and anti-vimentin in a biotin-streptavidin staining procedure. The renal cell carcinomas were classified according to the criteria of Fuhrman with a nuclear grading from I to IV. All carcinomas expressed cytokeratin, whereas co-expression with vimentin was present only in 53%. Expression for both intermediate filaments was present in aneuploid tumours with a marked nuclear pleomorphism and was more frequently related to a tubulo-papillary and pseudosarcomatous growth pattern. It is suggested that vimentin expression in renal cell carcinomas may be useful as a prognostic index in addition to nuclear grade. DNA content, mitotic rate and tumour stage.     

Heterogeneity of epithelial marker expression in routinely processed, poorly differentiated carcinomas.

The application of immunohistochemical markers against epithelial antigens has proved useful for studying tumor differentiation and in aiding tumor diagnosis. However, the reactivity of various epithelial markers with poorly differentiated carcinomas (the situation in which they are most often used) has not been well established. As a result, it is unclear how negative results should be interpreted and how often more than one antibody may be needed to document the epithelial nature of poorly differentiated neoplasms. We studied 98 poorly differentiated epithelial tumors with AE1, CAM 5.2, and EMA to assess the use of these markers in their diagnosis. Both CAM 5.2 and EMA provided support for epithelial differentiation in 71% (70/98) of the cases, while AE1 stained 50% (49/98) of the tumors; CAM 5.2 was the single most useful marker in the subset of poorly differentiated neuroendocrine carcinomas, staining 20 (77%) of 26 tumors. Use of these markers in pairs increased the recognition of epithelial differentiation (at least one marker showing positive staining) as follows: AE1/CAM 5.2, 80% (78/98); AE1/EMA, 87% (85/98); and CAM 5.2/EMA, 99% (97/98). Thirty carcinomas stained with all three markers, 34 with two markers, and in 34 cases only one antibody supported epithelial differentiation. Twelve (21%) of 58 tumors showed evidence of S100 reactivity. None of the 71 cases to which PD7 was applied showed staining This study indicates that poorly differentiated carcinomas are heterogeneous in their expression of antigens recognized by AE1, CAM 5.2, and EMA. Moreover, these results quantitate the probability of reactivity with poorly differentiated carcinomas for each marker and support the use of one or more antibodies in a "backup" panel when a negative result is obtained with a single antibody and the diagnosis of carcinoma is still suspected.     

Immunolocalization of 200 kDa neurofilaments in human cardiac endothelial cells

Neurofilaments usually associated with neural tissues are the type IV family of intermediate filaments. Nestin, which is a type VI intermediate filament, is a well known marker of endothelial cells in newly formed blood vessels and is developmentally and structurally related to type IV intermediate filaments. We aimed to determine whether or not cardiac endothelial cells (ECs) label with antibodies for neurofilaments (200 kDa, Novocastra-Leica, clone RT97), as is already known for nestin. We used cardiac samples (sinoatrial nodes/right atrial walls) from cadavers of normal and diabetic donors (6 normal adults, 10 type II diabetic adults, 1 child) for neurofilament immune labeling. Positive labeling of endothelial cells, microvascular and endocardial, was obtained in all samples. As this is the first such evidence, we can only presume that the neurofilament positive labeling of endothelial cells may be due to interactions of nestin and neurofilaments. Further studies are needed to evaluate the hypothesis we reached and, in order to explore whether or not neurofilament antibodies can qualify as markers of angiogenesis.     

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.     

Expression of intermediate filament proteins in adrenal cortex and related tumours

The intermediate filament profile of adrenal cortex and its related tumours has been evaluated. Most adrenocortical cells contained cytokeratin 8 and 18 as demonstrated by monoclonal antibodies CAM 5.2, M20, M9 and RGE53. Cytokeratin immunoreactivity was not confined to a functional zone of the adrenal cortex. Only a small number of the adrenocortical cells showed vimentin immunoreactivity. From normal adrenal cortex through adenomas, to carcinomas, there is a progressive decrease or even loss of cytokeratin immunoreactivity and an increase in vimentin immunoreactivity. Aberrant cytokeratin expression was not found in adrenocortical adenomas and carcinomas with the antibodies used. Awareness of the possible absence of cytokeratin immunoreactivity in adrenocortical carcinomas is important whenever antibodies to cytokeratins and vimentin are used for diagnostic purposes in poorly differentiated neoplasms.     

Synemin expression is widespread in liver fibrosis and is induced in proliferating and malignant biliary epithelial cells

The expression profile of intermediate filament proteins provides valuable information on the differentiation of specific cell populations and their contributions to disease. Synemin is one of the few intermediate filament proteins whose expression pattern during pathological situations is poorly characterized. We conducted a systematic immunohistochemical investigation of synemin expression in human liver diseases. In normal liver and in the early prefibrotic phase of chronic viral hepatitis or steatohepatitis, synemin was localized in hepatic stellate cells (HSCs) and vascular cells. Fibrotic or cirrhotic liver disease promoted intense synemin staining of HSCs in parenchymal and fibrous zones. In portal tract fibroblasts, synemin expression was rare under normal conditions but was widespread in severe inflammatory diseases associated with portal expansion, consistent with the notion that some fibrotic reactions involve HSCs, whereas others involve both HSCs and portal fibroblasts. Most sinusoidal endothelial cells were synemin negative in normal liver but were positive in hepatocellular carcinomas. Synemin was also expressed in the epithelial component of the ductular reaction in various liver diseases and in cholangiocarcinoma cells but not in hepatocellular carcinoma cells. Myofibroblasts in stromal reaction to carcinomas were synemin positive. Thus, synemin helps delineate different types of liver fibrotic reactions and provides a marker for sinusoidal capillarization and for proliferating biliary epithelial and cholangiocarcinoma cells.     

Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases

Aims:  To study caveolin-1 (Cav-1) expression in metastatic lung carcinomas.
Methods and results:  Cav-1 expression was investigated in a series of 121 lung carcinomas and it was shown that 18/121 tumours (14.9%) were Cav-1+. None of the pure bronchioloalveolar carcinomas proved to be positive, vs. 42.8% of the large cell carcinomas (neuroendocrine subtype excluded). Adenocarcinomas (8.5%), large cell neuroendocrine carcinomas (20%) and squamous cell carcinomas (29.6%) displayed an intermediate percentage of positive cases, suggesting a gradient of Cav-1 expression according to tumour histotype-related aggressiveness. Moreover, the percentage of Cav-1+ tumours with distant metastases was almost double that of non-metastatic tumours (17.8% vs. 8.1%), irrespective of the histotype. In 34 tumours metastatic to the brain, primary and secondary lesions were compared and 53% of brain metastases were Cav-1+ vs. 20.6% of primaries, indicating a de novo acquisition of Cav-1 expression. This pattern was exclusive to the brain, as it was not acquired in adrenal metastases. In our series, the presence of epidermal growth factor receptor amplification, determined by fluorescence in situ hybridization, was not related to Cav-1 reactivity.
Conclusions:  Cav-1 immunoreactivity in lung carcinoma is histotype-dependent and acquired de novo in brain metastases, suggesting a site-specific phenotypic shift in secondary lesions.     

Microtubule-associated protein-2: a new sensitive and specific marker for pulmonary carcinoid tumor and small cell carcinoma.

Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neuronally differentiated cells. Pulmonary neuroendocrine carcinomas such as carcinoid tumors and small cell carcinomas are derived from neuroendocrine cells. We hypothesize that neuroendocrine cells may also express MAP-2, and therefore, MAP-2 may be used as a marker for pulmonary carcinomas of neuroendocrine differentiation. To investigate the utility of using MAP-2 expression to separate pulmonary neuroendocrine from non-neuroendocrine tumors, we examined the expression of MAP-2 immunohistochemically in 100 cases of pulmonary carcinomas. The immunoperoxidase method with antigen retrieval was used to characterize the expression of MAP-2, chromogranin, synaptophysin, and neuron-specific enolase in 25 small cell carcinomas, 25 carcinoid tumors, 25 adenocarcinomas, and 25 squamous cell carcinomas. All tumors were lung primaries. All 25 cases of carcinoid tumors (100%) as well as 23 of 25 cases (92%) of small cell carcinomas were positive for MAP-2. Four of 25 cases (16%) of adenocarcinomas were positive for MAP-2 and synaptophysin. Among the 25 squamous carcinomas, 4 cases (16%) were positive for MAP-2, 2 cases (8%) were positive for synaptophysin, 11 cases (44%) were positive for neuron-specific enolase, and none was positive for chromogranin. In conclusion, MAP-2 is a new sensitive and specific marker for the pulmonary tumors of neuroendocrine differentiation. We recommend that MAP-2 be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors.     

Diagnostic value of intermediate filament antibodies in clinical cytology

Summary Antibodies to intermediate filament (IF) proteins can distinguish the major tumor groups as shown by results with sectioned human material. In this study we evaluate the use of similar methods in the cytology of human tumors. Smears obtained from fine needle aspiration biopsies were investigated using well characterized antibodies, each specific for only one of the five types of intermediate filaments. Tumor cells of different carcinomas, thymomas, and the epithelial part of pulmonary blastomas were positive with antibodies recognizing cytokeratins. Tumor cells in non-muscle sarcomas, including lymphoma and Ewing's sarcoma, could be specifically identified with antibodies to vimentin. Tumor cells of muscle sarcomas were desmin-positive. Finally, tumor cells in pheochromocytoma and bronchus carcinoid were positive with antibodies specific for neurofilaments. Specimens were also examined in parallel using conventional cytochemical stains, such as May-Grünwald-Giemsa. In addition, in most cases sections of the tumor were examined both by histology and IF typing of frozen sections to confirm the diagnosis made on the cytologic specimens. The results show that IF typing is a valuable diagnostic aid in clinical cytology.     

Diagnosing tumours on routine surgical sections by immunohistochemistry: use of cytokeratin, common leucocyte, and other markers

Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.