Immunohistochemical demonstration of lacto-N-fucopentose III in lung carcinomas with monoclonal antibody 624A12

Bronchopulmonary carcinomas were analyzed immunohistochemically using monoclonal antibody 624A12. The antibody was raised against a human "small cell carcinoma" cell line NCI-H69. It recognizes a particular sugar sequence in lacto-N-fucopentose III, which is preserved in formalin fixed and paraffin embedded tissue. Various bronchopulmonary carcinomas revealed characteristic patterns of immunoreactivity. Forty nine/50 adenocarcinomas were immunoreactive either diffusely or focally. The immunostaining was usually limited to the cell membranes with occasional intracytoplasmic immunostaining in large cells. The only negative case had been irradiated before surgical resection. Twenty seven/38 squamous cells carcinomas did not immunostain while the remaining 11 displayed focal immunoreactivity in areas of "loose cellular apposition" associated with necrosis and, rarely, in squamous pearls. All of six adenosquamous carcinomas showed immunoreactivity focally. Eleven/30 large cell carcinomas and 10/11 bronchiolo-alveolar carcinomas were either diffusely or focally immunoreactive. Seven/26 intermediate cell neuroendocrine carcinomas were focally immunoreactive while none of 33 typical small cell neuroendocrine carcinomas, 21 carcinoids, and 10 well differentiated neuroendocrine carcinomas was immunoreactive. An adenoid cystic carcinoma was diffusely immunoreactive, and a mucoepidermoid carcinoma was focally immunoreactive. We conclude that various bronchopulmonary neoplasms have characteristic patterns of distribution of this antigen, and that monoclonal antibody 624A12 may be useful for the differential diagnose among bronchopulmonary carcinomas, and their differential diagnosis from pleural mesotheliomas.     

Immunohistochemical demonstration of nonspecific cross-reacting antigen in normal and neoplastic human tissues using a monoclonal antibody. Comparison 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. Keratinizing 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.     

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.     

Malignant mesotheliomas. Improved differential diagnosis from lung adenocarcinomas using monoclonal antibodies 44-3A6 and 624A12.

Forty-three malignant pleural mesotheliomas and 10 known metastatic pulmonary adenocarcinomas to the pleura were studied by immunohistochemistry using monoclonal antibodies 44-3A6 and 624A12. Monoclonal antibodies 44-3A6 and 624A12 were raised against human pulmonary carcinoma cell lines; they recognize a membrane-associated protein of 40,000 mol wt and a specific sugar sequence of lacto-N-fucopentose III, respectively. Samples were also studied with a broad-spectrum antikeratin antibody and a polyclonal antibody to carcinoembryonic antigen (CEA). These investigations were performed on formalin-fixed and paraffin-embedded tissues. The mesotheliomas comprised only grossly evident, pleurectomized, or pneumonectomized cases; they included 22 epithelial, 15 biphasic, and 6 spindle cell types. Electron-microscopic study was also done on 9 cases. None of the mesotheliomas was immunoreactive to 624A12, while 9/10 metastatic pulmonary adenocarcinomas were convincingly immunoreactive. Monoclonal antibody 44-3A6 immunostained all of the metastatic adenocarcinomas strongly, whereas only 10/43 mesotheliomas were focally and weakly immunoreactive. The latter included 5 epithelial and 4 biophasic mesotheliomas and 1 spindle cell mesotheliomas; the immunoreaction was confined to scattered single cells, and the staining pattern was readily discernible from that of adenocarcinomas. Forty of 43 mesotheliomas were strongly immunoreactive with the broad-spectrum anti-keratin antibody, whereas 8/10 metastatic pulmonary adenocarcinomas showed focal and rather weak staining. Seven of 10 metastatic adenocarcinomas were immunoreactive to anti-CEA antibody, while only 15/43 mesotheliomas displayed weak immunoreactivity. It is concluded that monoclonal antibodies 44-3A6 and 624A12 are excellent phenotypic markers of metastatic pulmonary adenocarcinomas to the pleura and thus are useful for the differential diagnosis of pleural mesotheliomas. Given conventionally fixed and processed tissues, it appears that the combined use of these monoclonal antibodies may be more effective for that differential diagnosis than anti-CEA and anti-keratin antibodies.     

Differential distribution of the neuron-associated class III beta-tubulin in neuroendocrine lung tumors

OBJECTIVE: To study the immunoreactivity profile of the neuron-associated class III beta-tubulin isotype (beta III) in epithelial lung tumors. DESIGN: One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-beta III mouse monoclonal antibody (TuJ1) and an anti-beta III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. RESULTS: In the fetal airway epithelium, beta III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. beta III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, beta III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of beta III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal beta III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. beta III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of beta III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. CONCLUSIONS: In the context of neuroendocrine lung tumors, beta III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, beta III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, beta III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of beta III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.     

Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro

AIMS: To analyse the expression of alphavbeta6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. METHODS AND RESULTS: A new monoclonal antibody to the human beta6 subunit, 5C4, was used to locate alphavbeta6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of alphavbeta6 extracted from histological sections. Alphavbeta6 integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 +/- 0.52), followed by 24 intestinal-type gastric carcinomas (1.45 +/- 1.06) and eight lung adenocarcinomas (1.37 +/- 1.1). Moderate expression was found in 31 diffuse-type gastric carcinomas (0.94 +/- 0.83), seven duodenal adenocarcinomas (0.8 +/- 1.34) and 26 colorectal adenocarcinomas (0.76 +/- 0.71). Little alphavbeta6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well-differentiated carcinomas expressed more beta6 than poorly differentiated tumours. Peritumoral epithelial tissues where alphavbeta6-expressing tumours arose also expressed alphavbeta6. There was no correlation between expression of alphavbeta6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to alphavbeta6 up-regulation, but appeared independent of classical ligand binding to alphavbeta6. CONCLUSIONS: Our findings indicate that: (i) alphavbeta6 is overexpressed in pancreatic adenocarcinomas; (ii) alphavbeta6-positive carcinomas originate from alphavbeta6-expressing tissues; (iii) alphavbeta6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in-vitro overexpression of alphavbeta6 in pancreatic carcinoma cell lines accompanies spheroid formation.     

Pathological study of carbohydrate antigens in human lung cancer with monoclonal antibodies]

The expressions of carbohydrate antigens were examined with panel of specific anti-carbohydrate monoclonal antibodies (MAbs) on human lung cancer tissues. The MAbs used were SH1, SH2, SNH3, AH6, CA3F4, TKH2, TKH6 and TKH5 which define Lex, dimeric Lex, sialosyl Lex, Ley, Lea, sialosyl Tn, Tn and fucosyl GM1, respectively. Paraffin-embedded tissue sections (30 squamous cell carcinomas, 30 adenocarcinomas and 27 small cell carcinomas) were tested by immunohistological staining. Evaluation of stained specimens was performed by taking mean value of scores evaluated by three independent examiners. In squamous cell carcinoma, expression of Ley, sialosyl Tn, sialosyl Lex and Lea was significantly higher than other antigens. Lex was also expressed especially in keratinized tissues. In adenocarcinoma, Lea was expressed most remarkably. Sialosyl Lex, Ley, sialosyl Tn were also highly expressed in malignant cells. There was no significant difference in staining patterns between well and poorly differentiated adenocarcinomas. Sialosyl Tn and sialosyl Lex were positive in morphologically normal mucous glands adjacent to tumors. In small cell carcinomas, Ley was expressed more than other types of tumors, whereas Lex and sialosyl Tn were less than others. Tn antigen was observed throughout adenocarcinomas, squamous and small cell carcinomas in a relatively weak manner. Dimeric Lex and fucosyl GM1 antigens were not detected. Most of normal lung sections showed negative staining with those MAbs. These findings indicate that there are differential expressions of certain carbohydrate antigens in different types of human lung cancers based on their origins.     

Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by Immunohisto-chemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsln enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmlc localization of the protein in cells.     

Leu 7 immunoreactivity in fetal olfactory epithelium and dysplastic or neoplastic olfactory lesions induced in Syrian golden hamsters by N-nitrosodiethylamine.

The biotinylated monoclonal IgM antibody, anti-Leu 7 (HNK-1) was used to localize, by 2-step avidin-biotin immunocytochemistry, an antigen that appears in olfactory nasal epithelium of male Syrian Golden hamsters during N-nitrosodiethylamine (DEN) carcinogenesis. In normal young adult and adult hamsters, Leu 7 was not immunoreactive with nasal olfactory epithelium. In hamsters that had been given multiple doses of DEN, Leu 7 immunoreactivity was found throughout the olfactory epithelium. The carcinogen produced dysplastic and hyperplastic lesions in the olfactory epithelium as well as carcinoma in situ and poorly differentiated carcinomas, occasionally with rosette-like structures, all of which were immunoreactive with the Leu 7 monoclonal antibody. Other preneoplastic lesions and tumors (adenomas of nasal glands, papillomas, adenocarcinomas) in olfactory and respiratory nasal epithelium were never immunoreactive. Hamster fetuses expressed Leu 7 diffusely on olfactory epithelial cell membranes, neonatal hamsters had much less antigen, and 14- and 28-day-old hamsters contained few immunoreactive cells. Thus, evidence was provided that Leu 7 reacts with a fetal olfactory antigen which reappears during stages of chemically induced nasal carcinogenesis in Syrian Golden hamsters.     

Preservation of cluster 1 small cell lung cancer antigen in zinc-formalin fixative and its application to immunohistological diagnosis

Monoclonal antibodies reactive with cluster 1 small cell lung cancer antigen have been shown to be useful for the distinction of small cell from non-small cell tumours. In previous studies the antibodies have been applied to frozen sections and cold acetone-fixed tissues. However, one of three monoclonal antibodies that we produced, NCC-LU-243, reacted with some small cell lung carcinomas fixed in formalin solution and embedded in paraffin. The addition of zinc sulphate to the formalin solution at a concentration of 2% (v/w) greatly improved antigen immunoreactivity, and reactivity was retained even after prolonged fixation. Occasionally, immunoreactivity was present in a poorly differentiated adenocarcinoma with rosette-like structures. The monoclonal antibody NCC-LU-243 is thus of considerable potential value in the immunohistochemical diagnosis of small cell lung cancers.     

Incidence of latent infection of Epstein–Barr virus in lung cancers—an analysis of EBER1 expression in lung cancers by in situ hybridization

To evaluate the presence of Epstein–Barr virus (EBV) in lung cancers of Japanese patients, 81 lung cancers were examined using a highly sensitive in situ hybridization (ISH) method, employing an antisense oligonucleotide probe for EBV-encoded small nuclear RNA-1 (EBER). EBER1 expression was demonstrated in one poorly differentiated squamous cell carcinoma associated with marked lymphoid stroma (PDSCC-LS), two well differentiated adenocarcinomas, and two moderately differentiated squamous cell carcinomas, but was not detectable in other lung cancers, including small cell carcinomas. Unlike lymphoepithelioma-like undifferentiated carcinoma (LELC) of the lung, the PDSCC-LS consisted of poorly differentiated cells with distinct cell borders and nuclei with a coarse chromatin pattern and some prominent nucleoli. Most of the cancer cells expressed intense EBER1 signals. Although small to moderate numbers of cells positive for EBER1 were present in two adenocarcinomas and two squamous cell carcinomas, EBER1 signals varied in intensity and number in these four cases. Although polymerase chain reaction (PCR) and Southern blot hybridization with a ³²P-labelled probe internal to the primers were conducted to detect the EBV genome in 24 lung cancers, including five EBER1-positive cases, the genome was found to be positive in the five cases with EBER1-positive staining, including the PDSCC-LS, two adenocarcinomas and two squamous cell carcinomas, but not in the other cases. This study indicates that the morphological features of EBV-associated lung cancers are not restricted to the typical LELC type.     

Evaluation of CD43 expression in non-hematopoietic malignancies

ObjectivesCD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies.Methods17 tissue microarrays and sections from 19 individual cases were stained with CD43 (clone DF-T1) monoclonal antibody. The proportion of positive cells, stain localization (nuclear, cytoplasmic or membranous), and intensity (compared to internal leukocyte controls) were recorded in all cases.ResultsThere were 98/307 (32%) positive cases, that showed focal weak nuclear staining in 1–25% of cells, including 23/25 (92%) pancreatic ductal adenocarcinomas; 31/34 (91%) breast invasive ductal carcinomas; 13/15 (87%) papillary thyroid carcinomas; 3/4 (75%) follicular thyroid carcinomas; 6/15 (40%) renal cell carcinomas; 9/28 (32%) lung adenocarcinomas; 1/13 (8%) lung squamous cell carcinomas (SCCs); 2/8 (25%) prostate adenocarcinomas; 8/62 (13%) colon adenocarcinomas; and 2/21 (10%) neuroendocrine neoplasms. None of the positive cases demonstrated strong, membranous CD43 expression comparable to that seen in background mature lymphocytes or segmented neutrophils. Negative cases included 11 cervical SCCs, 12 cervical adenocarcinomas, 19 urothelial carcinomas, 10 lung small cell carcinomas, 11 sarcomas, and 19 poorly differentiated carcinomas from various tissue sites.ConclusionsIn our cohort, most non-hematopoietic neoplasms are negative for CD43 expression, with a subset showing focal, weak nuclear positivity. This data indicates that uniform and strong membranous staining appears to be specific to hematopoietic neoplasms.     

Polyclonal anti-PSA is more sensitive but less specific than monoclonal anti-PSA: Implications for diagnostic prostatic pathology

Prostate-specific antigen (PSA) production by nonprostatic tissues has been reported, casting doubts on its specificity. The immunohistochemical relative specificity and sensitivity of PSA expression using monoclonal and polyclonal anti-PSA was analyzed on 60 prostate carcinomas, 40 normal seminal vesicles, and 310 nonprostatic tumors. All nonprostatic tumors proved negative with both antibodies. However, 13 (32%) seminal vesicles showed immunoreactivity with polyclonal anti-PSA, but none showed immunoreactivity with the monoclonal antibody. The sensitivity of the 2 antibodies for prostate cancer varied with tumor grade. In Gleason pattern 3, both antibodies showed diffuse immunostaining in all cases. In Gleason pattern 5, polyclonal anti-PSA showed diffuse (>95%) tumor cell positivity in 18 cases (90%), while with the monoclonal antibody, 7 cases (35%) showed only focal (<10%) tumor cell immunoreactivity. Thus, monoclonal anti-PSA seems to be useful in small gland proliferations in which the differential diagnosis includes seminal vesicle, while for poorly differentiated neoplasms, polyclonal anti-PSA is considered superior. Sections of high-grade prostate cancer should be included as positive controls for PSA immunostaining.     

P53 immunohistochemical expression: messages in cervical carcinogenesis

AIMS: The pattern of p53 expression was studied in pre-invasive and invasive cervical carcinoma in an attempt to clarify its role in cervical carcinogenesis. METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were immunohistochemically studied for p53. RESULTS: p53 was detected more frequently in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1% invasive carcinoma) compared with benign cervices (P< 0.001); however, only three squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas and both adenosquamous carcinomas were poorly differentiated compared with one of the three squamous carcinomas. p53 immunoreactive cells were randomly distributed in invasive carcinoma, confined to the lower third of the epithelium in CIN I, reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III. CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. p53 was detected more frequently in CIN I compared with CIN II/III and invasive carcinoma which may be due to p53 protein degradation following interaction with high risk human papillomavirus E6 protein in CIN II/III and invasive carcinoma.     

The fine structure of large cell undifferentiated carcinoma of the lung. Evidence for its relation to squamous cell carcinomas and adenocarcinomas

The light microscopic diagnosis of large cell undifferentiated carcinoma of the lung is known to be highly subjective and shows poor interobserver reproducibility; the very existence of this tumor as a separate entity has been challenged. The ultrastructure of seven large cell undifferentiated carcinomas was examined in an attempt to determine whether they were merely poorly differentiated adenocarcinomas and squamous cell carcinomas, or actually represented an entirely separate class of tumors. Four large cell undifferentiated carcinomas demonstrated intra- and intercellular lumina and were designated adenocarcinomas. In three cases there were well formed desmosomes with numerous tonofilaments and intercellular bridges. These tumors were classified as squamous cell carcinomas. An eighth tumor metastatic to the abdominal wall also showed the features of squamous carcinoma. In addition, all tumors contained a variable population of primitive cells without identifying features. The large cell undifferentiated carcinomas were compared ultrastructurally with eight cases of poorly differentiated adenocarcinomas and squamous cell carcinomas classified by light microscopy. These tumors were morphologically similar, but contained fewer primitive cells and greater numbers of differentiated cells. Cells with a clear cytoplasm as seen by light microscopy were present in both the large cell undifferentiated and poorly differentiated groups; these cells contained variable amounts of glycogen but were otherwise similar to the nonclear cells. It is suggested that most of the subcategories of large cell undifferentiated carcinoma represent very poorly differentiated adenocarcinomas and squamous carcinomas.     

Immunoperoxidase staining for Ia-like antigens in paraffin-embedded tissues from human melanoma and lung carcinoma.

The human Ia-like antigens that are predominantly expressed by cells associated with immunologic function has been considered as a diagnostic marker of malignant transformation of some nonlymphoid tissues. Immunoperoxidase staining of formalin-fixed and paraffin-embedded tissue sections with a monoclonal antibody to Ia-like antigens was chosen for assessment of the value of this marker for diagnosis in surgical pathology. Monoclonal antibody LK8D3 developed against a human melanoma cell line bearing Ia-like antigens was found to react in serologic and immunochemical studies with an antigenic determinant of Ia-like antigens that was relatively stable to formalin fixation and paraffin embedding. Avidin-biotin complex peroxidase staining of formalin-paraffin sections with LK8D3 showed focal expression of Ia-like antigens in 3 of 12 melanomas, whereas all 8 cases of intradermal nevi were negative. Immunoperoxidase staining of formalin-paraffin sections of lung carcinomas with antibody LK8D3 was related to the histologic subtype of tumors. Thus, squamous cell carcinomas showed only very focal staining for Ia-like antigens in 5/9 cases, while widespread and intense Ia-like immunoreactivity was seen in 3/5 cases of lung adenocarcinomas, including two bronchioalveolar carcinomas. The presence of Ia-like antigens in lung adenocarcinoma may not be entirely associated with malignant transformation, because normal alveolar lining cells were stained with the antibody.     

肺腺癌和正常肺组织中抗p21ras单克隆抗体KGH-R1、KGH-R2、KGH-R3的免疫反应性比较

目的比较抗p21ras的单克隆抗体KGH-R1、KGH-R2、KGH-R3在肺腺癌和正常肺组织中的免疫反应性,为该抗体的临床应用奠定基础。方法用本实验室制备的广谱抗p21ras单克隆抗体KGH-R1、KGH-R2、KGH-R3对30例肺腺癌和30例正常肺组织进行免疫组化SP法染色,计算各样本的阳性细胞百分率和HSCORE分值,比较两组间的免疫反应性差异。结果单克隆抗体KGH-R1、KGH-R2、KGH-R3与肺腺癌发生免疫反应的百分率分别为83.33%(25/30)、93.33%(28/30)、63.33%(19/30);阳性样本的平均阳性细胞百分数均为100%;平均HSCORE评分分别为127.50分、280.25分、158.50分。与正常肺组织发生免疫反应的百分率分别为26.67%(8/30)、16.67%(5/30)、33.33%(10/30);阳性样本的平均阳性细胞百分数分别为7.75%、7.50%、8.05%;平均HSCORE评分分别为7.75分、7.50分、8.05分。单克隆抗体KGH-R1、KGH-R2、KGH-R3与肺腺癌免疫反应阳性样本的平均阳性细胞百分数比较,3者之间差异无统计学意义(P>0.05);3者阳性样本的平均HSCORE分值比较:KGH-R2比KGH-R1、KGH-R3有更强的免疫反应性(P<0.05)。结论 KGH-R1、KGH-R2、KGH-R3单克隆抗体与肺腺癌组织的免疫反应性强于正常肺组织,其中KGH-R2免疫反应性最强,可进一步开发为肺腺癌的治疗性抗体。