Immunohistochemical Demonstration of Nonspecific Cross-reacting Antigen in Normal and Neoplastic Human Tissues Using a Monoclonal Antibody: Cornparison with Carcinoembryonic Antigen Localization

Nonspecific cross-reacting antigen (NCA) immunoreactivity was localized in normal and neoplastic human tissues using a monoclonal antibody to 55, 90 and 95 kDa molecules of NCA. This was compared to the localization of immunoreactive carcinoembryonic antigen (CEA) as demonstrated by polyclonal and monoclonal antibodies. In frozen sections, CEA was localized in normal surface epithelium of the stomach and colon where NCA was only weakly detected. Type 1 and type 2 like pneumocytes were positive for NCA, while CEA was localized only in type 2-like pneumocytes. CEA and NCA were both demonstrated in ductal cells of frozen pancreatobiliary and mammary tissues. The antigenicity of CEA and NCA in normal tissues was significantly lost after paraffin embedding as compared to frozen sections. NCA was consistently demonstrated in eccrine sweat glands embedded in paraffin. In various tumor tissues, CEA and NCA were colocalized and expression increased sufficiently to be detected in paraffin sections. Adenocarcinomas of the stomach and colon and cystadenocarcinoma of the pancreas, as well as neuroendocrine carcinomas of the lung and thyroid, showed a CEA predominance over NCA. In ductal adenocarcinomas of the pancreas and breast and in cholangiocarcinoma, NCA reactivity was greater than CEA. Keratiniring foci of most squamous cell carcinomas of mucosal origin and some adenocarcinomas equally expressed both. Hepatocellular carcinoma, lobular mammary carcinoma and papillary thyroid carcinoma were positive only with unabsorbed polyclonal antibody which widely recognizes CEA-related substances. Renal cell carcinoma, prostatic adenocarcinoma, transitional cell carcinoma, anaplastic carcinomas, choriocarcinoma and basal cell carcinomas showed little or no immunoreactivity. Hence the relative ratio of CEA/NCA expression in tumors was dependent on the tissue of origin and histologic type. The cytoplasmic granular staining of NCA in cancer cells was a noteworthy difference from the plasma membrane-associated localization of CEA. Acta Pathol Jpn 40: 85–97, 1990.     

Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies.

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.     

Monoclonal antibodies against CEA-related components discriminate between pancreatic duct type carcinomas and nonneoplastic duct lesions as well as nonduct type neoplasias

Summary The expression of CEA and related antigens in formalin-fixed paraffin-embedded tissues of normal pancreas and different pancreatic neoplasms was studied immunocytochemically using three monoclonal antibodies (MAbs) recognizing different epitopes on CEA and related antigens. Additionally, a number of extrapancreatic malignancies were tested. The epitope recognized by MAb 250 (present on CEA and NCA 95) was expressed in all but one pancreatic ductal adenocarcinoma and ampullary carcinoma (42/43). The MAb 431 defined epitope (present only on CEA) was less frequently found (27/43). MAb 374, defining an epitope on CEA, NCA 95 and NCA 55 proved to be nearly as sensitive tive as MAb 250, but also reacted with normal duct epithelium. In contrast, MAb 250 and MAb 431 discriminated clearly between reactive duct lesions and malignant duct changes. Moreover, these MAbs differentiated between pancreatic duct carcinomas and nonduct type carcinomas as well as benign pancreatic tumours. In duct type carcinomas, the strongest staining was observed in well differentiated tumours. No discrimination was possible between pancreatic carcinomas and other adenocarcinomas of the gastrointestinal tract nor between most of the lung carcinomas and some other malignancies, specified below. MAb 250 and MAb 431 failed to react with hepatocellular carcinomas, renal cell carcinomas, carcinoids, sarcomas and melanomas. The findings suggest that paraffin-embedded tissues of pancreatic duct type carcinomas, in contrast to nonduct type tumours and normal ducts, are distinguished by the presence of a CEA and NCA 95 related epitope.Presented in part at the American Pancreatic Association Meeting, Chicago, 1984Supported by Deutsche Forschungsgemeinschaft Kl 366/4-1 and SFB 215     

Carcinoembryonic antigen and nonspecific cross-reacting antigen in medullary carcinoma of the thyroid

Carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) were studied immunohistochemically in formalin-fixed, paraffin-embedded tissues of 73 cases of medullary carcinoma of the thyroid (MTC) using 2 polyclonal antibodies (CEA antisera cross-reactive with or without NCA), 3 monoclonal antibodies recognizing epitopes only on CEA, and one monoclonal antibody against NCA. The staining patterns of the 5 antibodies against CEA in MTCs were not different, and they reacted with 86.3% of all cases. With regard to the effects of fixatives on the staining patterns, samples fixed with formalin or 4% paraformaldehyde demonstrated CEA immunoreactivity in both the cell membrane and cytoplasm. In Bouin-fixed tissue, the immunoreactivity was predominant on the cell membrane, whereas cytoplasmic positivity predominated in alcohol-fixed specimens. Thus the difference in fixatives used in previous studies does not appear to be a major reason for the difference in the reported incidence of CEA-positive MTCs. It is concluded that CEA is still a useful tumor marker for MTC and that it is detectable only in thyroid tumors originating from C cells, as seen in our series. The epitope defined by monoclonal antibody F106-88, present only on NCA, was found in 42.5% of all cases (49.2% of CEA-positive MTCs). The NCA immunoreactivity was located in the tumor cell cytoplasm as globular aggregates, which were also labeled for CEA.     

Carcinoembryonic Antigen and Nonspecific Cross-reacting Antigen in Medullary Carcinoma of the Thyroid

Carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) were studied immunohisto-chemically in formalin fixed, paraffin embedded tissues of 73 cases of medullary carcinoma of the thyroid (MTC) using 2 polyclonal antibodies (CEA antisera cross-reactive with or without NCA), 3 monoclonal antibodies recognizing epitopes only on CEA, and one monoclonal antibody against NCA. The staining patterns of the 5 antibodies against CEA in MTCs were not different, and they reacted with 86.3% of all cases. With regard to the effects of fixatives on the staining patterns, samples fixed with formalin or 4% paraformaldehyde demonstrated CEA immunoreactivity in both the cell membrane and cytoplasm. In Bouin fixed tissue, the immunoreactivity was predominant on the cell membrane, whereas cytoplasmic positivity predominated in alcohol fixed specimens. Thus the difference in fixatives used in previous studies does not appear to be a major reason for the difference in the reported incidence of CEA positive MTCs. It is concluded that CEA is still a useful tumor marker for MTC and that it is detectable only in thyroid tumors originating from C cells, as seen in our series. The epitope defined by monoclonal antibody F106 88, present only on NCA, was found in 42.5% of all cases (49.2% of CEA positive MTCs). The NCA immunoreactivity was located in the tumor cell cytoplasm as globular aggregates, which were also labeled for CEA.     

Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.     

Immunohistochemistry of CEA in the human pancreas during development, in the adult, chronic pancreatitis, and pancreatic adenocarcinoma

This study describes the immunohistologic distribution of carcinoembryonic antigen (CEA) in 30 fetal pancreata, 5 normal adult pancreata, 11 cases of chronic pancreatitis without carcinoma, 16 cases of chronic pancreatitis with carcinoma, and 20 cases of primary pancreatic adenocarcinoma. The position of CEA-cross-reacting antigen, especially of nonspecific cross-reacting antigen (NCA), was also studied in the case of chronic pancreatitis and pancreatic adenocarcinoma. For this purpose, both monospecific antibodies to CEA and NCA, as well as cross-reacting antibodies, were used in an indirect immunoperoxidase technique. CEA reactivity could not be detected, neither during pancreatic development nor in chronic pancreatitis with or without associated adenocarcinoma. In 15 of 20 pancreatic adenocarcinomas, CEA positivity was found both with membranous and cytoplasmic localization. With the use of the cross-reacting antibodies, all cases of chronic pancreatitis and pancreatic adenocarcinomas showed positive staining of both ductal and tubular structures. Antibodies to NCA closely mimicked the results obtained with the cross-reacting antibodies both in pancreatitis and adenocarcinoma. From the authors' results it can be concluded that CEA is not a developmental antigen of the pancreas. Furthermore, NCA cross-activity of anti-CEA antibodies is an important reason of false positive reaction in chronic pancreatitis. Moreover, true CEA positivity in the pancreas appears to be restricted to adenocarcinoma of the exocrine pancreas.     

Conserved antigen expression in epithelial tumors recognized by monoclonal antibody 4A9 generated against canine mammary carcinoma cells

Hybridoma-derived murine monoclonal antibodies (MoAbs) were generated by fusing P3X63-Ag8.653 myeloma cells with splenic cells from BALB/c mouse which had been immunized with viable canine mammary adenocarcinoma cells, CMT-2. Fifteen MoAbs were shown to react with immunizing cells in indirect immunofluorescence (IFA) and enzyme-linked immunosorbent (ELISA) assays. The reactivity of one IgM MoAb, designated 4A9, was evaluated. The antigen recognized by 4A9 on CMT-2 cells appeared to be localized both in cell membrane and cytoplasm against fixed and unfixed preparations by IFA. The 4A9 MoAb was found to bind with four of five canine mammary carcinoma cell lines while no binding was detected with normal fibroblastic cell lines. In vivo tissue distribution of 4A9 antigen was evaluated by indirect immunoperoxidase (IP) assay against formalin-fixed, paraffin-embedded sections of normal and neoplastic tissues. 4A9 MoAb reacted strongly to moderately with 75% of mammary carcinomas, moderately to weakly with 57% of benign mammary tumors, and strongly with squamous cell and perianal gland carcinomas (100%), interstitial cell tumors (100%), transitional cell carcinomas (43%), lung adenocarcinomas (40%), colon carcinomas (33%), and pancreatic adenocarcinomas (20%). Moderate to weak staining was detected with granulosa cell tumors (25%) and apocrine gland adenocarcinomas (50%). Strong reactivity with perianal gland carcinomas contrasted to no reactivity with perianal gland adenomas. No immunostaining was detected with a large variety and number of normal adult and fetal tissues tested; negligible and very restricted staining was observed in a few adult and fetal tissues. Normal mammary gland was negative. Since the antigen is expressed on the cell surface and in the cytoplasm of most mammary carcinoma cells and a variety of other epithelial tumor cells, the 4A9 antibody may have potential application in diagnosis and management of canine mammary cancer and a variety of other epithelial tumors.     

Immunocytochemical localization of carcinoembryonic antigen in benign and malignant colorectal tissues. Assessment of diagnostic value

Immunoperoxidase and immunofluorescence staining for carcinoembryonic antigen (CEA) was performed on paraffin and frozen sections, respectively, of colonic carcinomas (70), liver and lymph node metastases (20), mesenteric nodes (150), mucosa adjacent to carcinoma (40), colonic resection margins (20), normal colon (ten), and colorectal polyps (64) in order to assess its potential diagnostic value. On the basis of this study of the immunocytochemical localization of CEA in colorectal tissues, conclusions were as follows. (1) Localization of CEA to glycocalyx of surface epithelial cells is a normal finding in the colon and is similar in normal colon and mucosa distant and adjacent to infiltrating carcinoma. (2) Although strongly positive cell surface and intraluminal staining frequently correlates with the presence of carcinoma in neoplastic polyps, it is not by itself a reliable diagnostic criterion. (3) Failure to demonstrate CEA in a gland-forming carcinoma makes a diagnosis of colorectal carcinoma unlikely. (4) Poorly differentiated colorectal carcinoma usually contains much less demonstrable surface CEA, but may occasionally stain cytoplasm strongly. (5) Although lymph node micrometastases from colorectal carcinoma are readily demonstrated by immunoperoxidase staining for CEA, screening of hematoxylin and eosin-stained sections by a competent pathologist appears to be adequate for their detection.     

Vimentin expression in benign and malignant breast epithelium.

AIMS--To determine vimentin expression in epithelial cells in benign breast disease and malignant breast tumours; to assess the value of vimentin expression as a prognostic indicator in breast carcinoma. METHODS--Frozen and formalin fixed, paraffin wax embedded sections from 78 carcinomas, three phyllodes tumours, 19 fibroadenomas and 19 cases of fibrocystic disease were examined with a monoclonal antibody from the V9 clone. A correlation between vimentin expression and known prognostic indicators was sought in ductal carcinomas. The intracellular localisation of vimentin was examined in benign and malignant lesions. RESULTS--Vimentin expression was identified on frozen section in the cells of ductal (53%), lobular (86%), and mucinous (33%) carcinomas and in the luminal epithelium of fibroadenomas (68%), cases of fibrocystic disease (47%), and a malignant phyllodes tumour. Formalin fixation reduced the percentage of carcinomas and cases of benign disease in which vimentin was detected. This reduction was more pronounced in fibroadenoma and fibrocystic disease than in ductal carcinoma. Associations were identified between vimentin expression as detected on frozen section and tumour grade, size, number of lymph nodes affected, oestrogen receptor content and growth fraction. Only the association with grade was significant (p = 0.045). There was no significant correlation between any of these prognostic variables and vimentin expression on paraffin wax sections. There was no difference in the intracellular localisation of vimentin staining between benign and malignant lesions, or between low and high grade ductal carcinomas. CONCLUSION--There is some loss of vimentin immunoreactivity after formalin fixation. Vimentin expression does not assist in differentiating between benign and malignant breast disease, but is correlated with tumour grade in ductal carcinoma.     

Correlation of carcinoembryonic antigen in tissue sections with spread of mammary carcinoma

An immunoperoxidase technique for the histological demonstration of Carcinoembryonic Antigen (CEA) was applied to paraffin sections from 74 breast carcinomas and 43 benign breast lesions. Sixty-six per cent of the carcinomas and the only case of granular cell myoblastoma examined were CEA positive. Two examples of mammary dysplasia (7%) showed foci of CEA positive acini. All tumour tissue found in lymphatics and in metastases in lymph nodes was CEA positive, including two cases where the primary tumour was CEA negative, and all the metastases examined from CEA positive tumours. A significant relationship was found between CEA positivity of the primary tumour and the presence of lymph node metastases.     

Analysis of the tumour-associated antigen TAG-12 by monoclonal antibody 7A9 in normal,benign and malignant mammary tissues

Summary A monoclonal antibody 7A9 was raised against the tumour-associated glycoprotein TAG-12 purified from T47-D breast carcinoma cells. In immunoblots from cytosol of T47-D cells and from sera of breast cancer patients, antibody 7A9 detects the high molecular weight mucin-like TAG-12 antigen. A series of paraffin sections of normal, benign and malignant mammary tissues have been studied with monoclonal antibody 7A9 and the immunoalkaline phosphatase method. In resting gland, proliferating gland and fibroadenoma ducts, reactivity of 7A9 was mainly restricted to luminal membranes of epithelial cells and secretions. 77/79 primary breast carcinomas including ductal, lobular and various other carcinoma types showed cytoplasmic and/or membrane-associated staining with 7A9 in most tumour cells. Metastases (31/31) from different sites were also positive. Strong immunoreactivity with single tumour cells was noted in cytological preparations from freshly resected breast cancer tissue. Thus, monoclonal antibody 7A9 seems to be very useful for the targeting of breast carcinoma cells.     

Pancreatic ductal adenocarcinomas with cystic features: neither rare nor uniform.

Cystic tumors of the pancreas are uncommon but important because of their diverse pathology and biology. Their wide spectrum also includes cystic variants of otherwise solid tumors, such as cystic endocrine tumors, cystic acinar cell carcinomas and ductal adenocarcinomas with cystic changes. In this study, we screened pancreatic ductal adenocarcinomas and their variants for macrocystic changes and determined the nature of the cysts (neoplastic vs non-neoplastic). Of 483 tumors 38 (8%) had cystic features. The largest group consisted of 24 pancreatic ductal adenocarcinomas showing a large-gland pattern with small cysts whose diameter varied between 0.5 and 1.8 cm. The epithelial lining of these cysts was generally positive for CEA (83%) and/or MUC1 (71%) and MUC5AC (74%). p53 was positive in 57% of the cases. The second group of cystic tumors (8/483) showed degenerative cystic cavities with diameters ranging between 1 and 6 cm. This group consisted of poorly differentiated pancreatic ductal adenocarcinomas, undifferentiated carcinomas with or without osteoclast-like giant cells and one adenosquamous carcinoma. In the third group of cystic tumors there were four pancreatic ductal adenocarcinomas containing tumor-related retention cysts. Their epithelial cells were positive for MUC5AC, but negative for CEA, MUC1 and p53. The fourth group consisted of two pancreatic ductal adenocarcinomas showing closely attached pseudocysts caused by tumor-associated pancreatitis. The results indicate that a considerable number of pancreatic ductal adenocarcinomas and their variants display cystic features and must therefore be considered in the differential diagnosis of cystic neoplasms of the pancreas. Moreover, not all of the cystic structures we observed were neoplastic in nature. They may also represent non-neoplastic changes, such as retention cysts and inflammatory pseudocysts.     

Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas on paraffin sections

CD56 is immunohistochemically detectable in virtually all small cell carcinomas on frozen sections. The authors retrospectively tested the usefulness of the monoclonal antibody 123C3 against CD56 to differentiate pulmonary and extrapulmonary small cell carcinomas from nonneuroendocrine non—small cell carcinomas by paraffin-section immunohistochemistry after antigen retrieval. The study included 70 small cell carcinomas and 344 primary and metastatic nonneuroendocrine carcinomas of various primary sites. The staining results were compared with specific neuroendocrine markers (CD57, Chromogranin A, Synaptophysin). The monoclonal antibody 123C3 diffusely stained most small cell carcinomas with a strong membranous pattern (sensitivity: 0.99). The staining intensity was not diminished in areas with crush artifacts or after decalcification. The neuroendocrine markers had a combined sensitivity of only 0. 44 for small cell carcinomas. With regard to nonneuroendocrine carcinomas, the 123C3 antibody stained 7 of 28 ovarian carcinomas, 6 of 30 renal cell carcinomas, 2 of 10 endometrial carcinomas, two of three nonneuroendocrine large cell carcinomas of the lung, 1 of 38 adenocarcinomas, and 4 of 52 squamous cell carcinomas of the lung. Urothelial carcinomas, hepatocellular carcinomas, squamous carcinomas of the head/neck and cervix uteri, as well as adenocarcinomas of the breast, stomach, colon, pancreas, and prostate, showed no immunoreactivity for CD56. The specificities of 123C3 and the combined neuroendocrine markers for small cell carcinomas were 0. 94 and 0. 95, respectively. The authors conclude that monoclonal antibody 123C3 might be useful for the immunohistochemical differentiation of small cell carcinomas from nonneuroendocrine carcinomas on paraffin sections, especially in small and crushed biopsy specimens.     

Immunohistochemical analysis of p53 protein expression in benign and malignant skin tumors using a panel of anti-p53 antibodies.

The expression of p53 in a variety of benign and malignant skin lesions has been first assessed in frozen sections and then compared with the results obtained in corresponding paraffin-embedded sections using various immunohistochemical staining methods with a panel of anti-p53 antibodies. Of the 48 benign and malignant skin lesions studied, 46(96%) had corresponding paraffin sections and immunohistochemical results obtained with DO7 on frozen and paraffin sections were concordant in 97%, qualitatively. Using streptavidin-biotin complex method, p53 was identified in 33% of dysplastic squamous lesions, 50% of squamous cell carcinomas (SCCs) and 36% of basal cell carcinomas (BCCs) on frozen section, whereas 25% of dysplastic squamous lesions, 40% of SCCs, and 32% of BCCs showed p53 positivity on paraffin-embedded sections. In frozen sections, the same regions of each specimen exhibited similar topographic patterns of positive immunoreactivity with both monoclonal antibodies, PAb 1801 and DO7. In contrast, immunohistochemical staining with polyclonal antibody, CM-1, gave poor morphologic resolution, although effective in paraffin-embedded sections.     

Cervical carcinoma antigen, carcinoembryonic antigen (CEA), and nonspecific cross-reacting antigen (NCA) in appraisal of uterine cervix smears

The distribution of cervical carcinoma antigens (AgCaCx), CEA, and NCA in different pathologic states of the uterine cervix was studied in cytologic smears by an immunofluorescence method (IF) using specific immune sera against perchloric acid (PCA) extract of cervical squamous cell carcinoma, anti-CEA, and anti-NCA. After excluding cross-reactivity with CEA and NCA, the presence of AgCaCx was demonstrated in the majority of cervical carcinomas, severe dysplasias, and only in one-fourth of squamous metaplasias, especially when accompanied by mild or moderate dysplasias. The intensity and percentage of IF-positive cells varied from case to case. The preparations of uterine cervix without pathologic changes usually were negative. Similar results were obtained with anti-CEA serum. NCA was present in the majority of smears independent of histologic diagnosis. The most intense fluorescence was observed in upper layers of the epithelium. NCA could be a differentiation antigen of stratified squamous cell epithelium.     

Immunohistochemical analysis of the distribution of a breast tumor associated antigen recognized by a monoclonal antibody.

A new monoclonal antibody (MoAb), MM 1-80, recognizing a tumor associated epitope of a breast high molecular weight mucin molecule was tested, using the avidin biotin immunoperoxidase method on normal and pathological mammary tissues. The normal mammary ducts and lobules were negative. Fibroadenomas showed a strong intracytoplasmic staining. In apocrine metaplasia, adenosis, and papillomatosis, scattered cells showed intracytoplasmic, luminal border or secretion reactivity. In lobular and ductal hyperplasia the cells showed intracytoplasmic immunoreactivity which, however, became more intense and homogeneous in atypical lesions, i.e. lobular and ductal in-situ carcinomas. The infiltrating carcinomas of different histotype expressed positivity on 98% of the cases (113/115) and axillary metastatic lymph nodes were always positive (20/20). The MoAb was tested on 175 human neoplasias of different origin which were in the majority of the cases negative with the exception of adenocarcinomas of the lung, ovary and bladder. MM1-80 appears to react preferentially with mammary cells undergoing hyperplastic, metaplastic and neoplastic processes. The 1-80 epitope distribution is different in these lesions starting with a predominant luminal expression in benign lesions and becoming strong and cytoplasmic in the malignant breast cell.     

p53 protein expression in fine-needle aspirates of breast cancer: An immunocytochemical assay for identifying high-grade ductal carcinomas

The expression of the p53 gene product was investigated immunocytochemically in a series of 51 fine-needle aspiration (FNA) samples of breast carcinomas. Results were compared with those obtained by immunocytochemistry on paraffin embedded tissue sections of the corresponding surgical specimens. Cytological samples showed a variable degree of p53 immunoreactivity in 14 tumors (27.6%), all of ductal type, while p53 immunoreactive tumor cells were present in tissue sections from 15 carcinomas (29.4%). The only discordant case was a signet-ring cell carcinoma. Abnormal p53 expression was significantly associated with high nuclear grade in ductal carcinomas. No association was seen with tumor size, lymph node status, and age of the patient. Detection of p53 altered expression in FNA samples of breast carcinoma may play a role in the assessment of tumoral grading and is predictive of p53 immunoreactivity in histological specimens. © 1995 Wiley-Liss, Inc.