A panel of antibodies useful in the cytologic diagnosis of metastatic melanoma.

Five antibodies, 2D.1 (pan-leukocyte), AE-1,3 (anti-keratin), B72.3 (anti-carcinoma), ME 1-14 (alpha-chondroitin sulfate proteoglycan) and polyclonal S-100 protein (P-S100), were tested to determine if this panel could be used immunocytochemically to differentiate melanoma from nonmelanoma. A total of 161 cases were evaluated: 145 fine needle aspirates of various body sites and 16 effusions, consisting of 52 melanomas, 41 adenocarcinomas, 11 squamous cell carcinomas, 14 undifferentiated carcinomas, 8 small cell carcinomas, 8 miscellaneous carcinomas, 8 primary central nervous system (CNS) tumors, 7 lymphomas/leukemias, 4 sarcomas and 8 benign effusions. The 52 melanomas were stained by ME 1-14 (in 31 cases) and by P-S100 (in 39 cases), but not by B72.3, AE-1,3 or 2D.1. The 82 carcinomas reacted with P-S100 (in 25 cases), B72.3 (in 37 cases), AE-1,3 (in 68 cases) and 2D.1 (in 1 case), but not with ME 1-14. Lymphomas were stained only by 2D.1 (5 of 7 cases). The eight primary CNS tumors reacted solely with ME1-14 (in 3 cases) and P-S100 (in 3 cases). The eight benign effusions exhibited staining by ME 1-14 (in 1 case), P-S100 (in 1 case), AE-1,3 (in 3 cases) and 2D.1 (in 8 cases), but not by B72.3. Thirty-six cases (including 11 melanomas) failed to stain with any antibody. In summary, 41 of 52 melanomas and 4 of 8 CNS tumors stained with ME1-14, P-S100 or both and were negative for B72.3, AE-1,3 and 2D.1. Only 2 of 101 other nonmelanomas exhibited this pattern. Thus, this panel distinguishes melanoma from other neoplastic and nonneoplastic processes in the majority of cases.     

Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms

We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.     

Simultaneous immunoenzyme staining of vimentin and cytokeratins with monoclonal antibodies as an aid in the differential diagnosis of malignant mesothelioma from pulmonary adenocarcinoma

The occurrence and coexpression of the cytoskeletal proteins vimentin and cytokeratins were studied in malignant mesotheliomas and pulmonary carcinomas. For this purpose a double immunoenzyme staining with monoclonal antibodies was developed which made it possible to visualize vimentin and cytokeratins simultaneously within the same cell. A clear distinction between stromal cells (vimentin only) and tumour cells was also obtained. A total of 12 mesotheliomas (six mixed type and six epithelioid type) and 13 carcinomas (eight adenocarcinomas and five large cell undifferentiated carcinomas) were studied. The results revealed a clear difference between mesotheliomas and adenocarcinomas: 11 of 12 mesotheliomas showed coexpression of vimentin and cytokeratins in at least 50% of the tumour cells, while in seven of the eight adenocarcinomas none or only a few cells could be seen with this coexpression. In the undifferentiated large cell carcinomas three of five expressed both components, but in less than 25% of the cells. It is concluded that a reliable double immunoenzyme staining of vimentin and cytokeratins can be used as an additional means to distinguish malignant mesothelioma from pulmonary adenocarcinoma.     

Morphologic and immunocytochemical studies of bronchioloalveolar carcinoma at Duke University Medical Center, 1968-1986

Between 1968 and 1986, the tumor registries at Duke University Medical Center and Durham VA Medical Center accumulated a total of 193 patients with a diagnosis of bronchioloalveolar carcinoma (BAC). All available histologic sections of primary lung tumors and all available respiratory and pleural cytologic material were reviewed for 135 cases having an initial histologic diagnosis of BAC and no history of a primary nonpulmonary adenocarcinoma. Thirty-nine cases showed a pure BAC pattern in histologic sections; 76 showed a dominant BAC pattern with focal areas of fibrosis and acinar differentiation; 16 were carcinomas with a focal BAC pattern; and 4 were adenocarcinomas lacking a BAC pattern. Of the 115 cases with at least a dominant BAC pattern, 51 showed predominantly mucinous differentiation while 64 showed predominantly nonmucinous differentiation. Adequate cytologic material was available for review from 111 patients. For cases having at least a dominant BAC pattern, tumor cells were present in 77 of 172 adequate sputums (44.8%), 36 of 133 bronchoscopy specimens (27.1%), 15 of 18 needle aspirates (83.3%) and 14 of 15 pleural fluids (93.3%). Of all patients in this group, 60.2% had at least one specimen positive for malignancy. No cytologic features clearly distinguished adenocarcinomas having only focal bronchioloalveolar differentiation from those with a pure or dominant BAC pattern. A significant degree of overlap was observed in the cytologic features of mucinous and nonmucinous tumors. Histologic sections from 19 mucinous and 16 nonmucinous tumors were stained with monoclonal antibody B72.3: all showed some staining, with no significant difference in degree of staining between the two groups. This suggests that expression of the tumor-associated glycoprotein TAG-72 is independent of mucinous differentiation.     

CK5/6 in effusions: no difference between mesothelioma and pulmonary and nonpulmonary adenocarcinoma

OBJECTIVE: To test the performance of CK5/6 for the differentiation between mesothelioma, adenocarcinoma and benign mesothelia/proliferations in effusion cytology. STUDY DESIGN: CKS/6 immunocytochemistry was applied to ethanol-fixed cytospin preparations from 74 benign and malignant effusions. RESULTS: Reactivity was seen in 7 of 8 mesotheliomas and in 9 of 11 benign mesothelial proliferations but also in 11 of l7 pulmonary adenocarcinomas and in 12 of 31 adenocarcinomas of nonpulmonary origin. Reactivity was also found in 3 of 5 non-small cell lung carcinomas and 1 of 1 squamous carcinoma. CONCLUSION: CK5/6 reactivity was found in a considerable proportion of metastatic adenocarcinomas of pulmonary and nonpulmonary origin. The high reactivity rate in pulmonary adenocarcinomas disagrees with the results obtained with histologic sections from solid tumor tissue, and CK5/6 seems to be of very limited value as an additional marker in effusion cytology.     

Applications of monoclonal antibodies in clinical cytology as exemplified by studies with monoclonal antibody B72.3. The George N. Papanicolaou award lecture

The monoclonal antibody (MAb) B72.3, reactive with a high-molecular-weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been previously shown to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct for the diagnosis of carcinoma in cell blocks and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from all of 21 patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions from 41 patients. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected adenocarcinoma cells in effusion specimens from 12 of 12 patients with adenocarcinoma of the lung and 16 of 16 patients with adenocarcinoma of the ovary. MAb B72.3 has recently been used with fine needle aspiration (FNA) biopsy specimens and the corresponding surgically excised tumors to determine cellular reactivity. Using the ABC immunoperoxidase method, fine needle aspirates and corresponding surgically excised tumors were analyzed for TAG-72 expression. Positive staining with MAb B72.3 was observed in needle aspirates of 27 of 27 adenocarcinomas and adenosquamous carcinomas of the lung, 17 of 21 adenocarcinomas of the breast, 6 of 6 adenocarcinomas of the colon and in carcinomas from other body sites. In contrast, 21 small-cell carcinomas of the lung, 13 malignant melanomas, 2 lymphomas and 2 sarcomas did not stain with the antibody. Benign lesions from the breast, lung, pancreas, parotid and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B72.3. In more than 90% of these patients, the staining patterns of the tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies, it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, that is most selectively expressed in carcinomas and that may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in fine needle aspiration biopsies.     

The establishment of two rat colonic carcinomas in tissue culture. A basic prerequisite for standardized experiments on the biology of colonic carcinomas in vivo

Two rat colonic carcinomas (DMH-Co-1 and DMH-Co-2) derived from dimethyl-hydrazine-induced metastasizing adenocarcinomas were established as permanent cell lines. By means of electron microscopy, immunofluorescence microscopy and biochemical analysis of cytoskeletal components, it has been shown that both tumor cell lines retain in vitro the phenotypic characteristics of the primary tumors. The in vitro growth properties revealed only minor differences between the two cell lines. After retransplantation in vivo, DMH-Co-2 gave rise to moderately differentiated adenocarcinomas, whereas the tumors arising from DMH-Co-1 exhibited a continuum of differentiation encompassing adenocarcinomas, undifferentiated carcinomas and squamous cell carcinomas. These permanent cell lines offer the opportunity for isolating divergent subpopulations by in vitro cloning and facilitate standardized experiments on their biological behaviour in vivo.     

Is agNOR and DNA ploidy analysis useful for evaluating thyroid neoplasms?

OBJECTIVE: To correlate the subjective AgNOR counting method and DNA content with histologic diagnoses of thyroid cancer and invasion. STUDY DESIGN: Eighty-one consecutive cases of thyroid carcinoma were selected for DNA and AgNOR analysis. The diagnoses were: papillary carcinoma (n = 40), follicular carcinoma (n = 31), Hürthle cell adenocarcinoma (n = 4), and undifferentiated carcinoma (n = 6). Seven normal thyroids were used as controls. DNA quantitative measurement was performed with Vidas 2.0 software (Kontron Bildanalyse, Munich, Germany) connected to an MPM 210 photometer microscope (Carl Zeiss, Oberkochen, Germany). The DNA index was obtained using histograms. Counting the NORs was performed by subjectively counting the NORs in 200 malignant cells. RESULTS: DNA ploidy analysis showed all Hürthle cell adenocarcinomas, 21 (67%)follicular tumors, 23 (57%) papillary tumors and 4 (67%) undifferentiated carcinomas to be aneuploid. DNA analysis correlated with histologic type of the tumor (p = 0.032). There was no statistical significance to the AgNOR counting variables studied. Statistical analysis showed correlation between ploidy and histologic diagnosis, but not AgNOR counting, to have prognostic value. CONCLUSION: DNA ploidy is more useful than subjective counting of NORs as an adjunct method for thyroid lesion analysis.     

Expression of keratin 5 as a distinctive feature of epithelial and biphasic mesotheliomas. An immunohistochemical study using monoclonal antibody AE14

In previous biochemical analyses, keratin 5 (Mr 58,000) has been detected in most mesotheliomas with epithelial component but not in pulmonary adenocarcinomas (Blobel et al., Am J Pathol 121: 235-247, 1985). In the present study, we have characterized a monoclonal antibody, AE14, as being selectively specific for keratin 5 (apart from the reactivity with certain hair proteins) as shown by immunoblotting of gel-electrophoretically separated proteins from various tissues. Immunohistochemical screening of a variety of normal human tissues, using immunoperoxidase microscopy on cryostat sections, revealed the binding of this antibody to the basal, immature cells of stratified squamous epithelia, to basal cells of pseudostratified epithelia, to some myoepithelial cells, thymic reticulum cells, certain pancreatic duct cells, as well as a variable subpopulation of mesothelial cells of the pleura and the peritoneum. In 12/13 epithelial and biphasic mesotheliomas of the pleura, heterogeneous but extended staining with antibody AE14 was seen whereas 21 pulmonary adenocarcinomas were negative or, in six of these cases, showed staining of only a few cells. Among carcinomas from other sites, colonic adenocarcinomas and renal cell carcinomas were negative whereas limited staining was found in some pancreatic adenocarcinomas. It is suggested that antibody AE14 may be useful, as a defined polypeptide-specific reagent, in the histologic distinction between mesotheliomas and most adenocarcinomas. Furthermore, the expression patterns of keratin 5 as detected by antibody AE14 in various normal and malignant epithelial tissues are discussed, particularly their relation to processes of squamous metaplasia and their indication of phenotypic tumor heterogeneity.     

Immunohistochemical studies with monoclonal antibodies B72.3 and MA5 on histologic and cytologic specimens from benign and malignant breast lesions

Monoclonal antibodies B72.3 and MA5 were tested by the avidin-biotin immunoperoxidase method in histologic sections of 38 benign, 22 precancerous and 22 cancerous breast lesions, as well as in fine needle aspiration (FNA) smears and cell blocks of 25 breast carcinomas. Neither B72.3 nor MA5 was specific for breast cancer cells: both also reacted with cells from benign and precancerous conditions. B72.3 as a "detector" of malignant cells or their precursors was superior to MA5, however: it was not reactive to cells in most benign breast lesions (mammary duct ectasia, fibroadenoma and ductal hyperplasia, with and without atypia). Cancerous cells had heterogeneous immunostaining with B72.3, which may lead to false-negative results in relatively hypocellular FNA samples. FNA samples prepared as both smears and cell blocks provided the most abundant cellular samples and the lowest false-negative immunostaining reaction of cancerous cells with B72.3.     

Optimal immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissue requires preliminary trypsinization. An immunoperoxidase study of various tumours using polyclonal and monoclonal antibodies

The effect of preliminary trypsinization on the immunoreactivity of keratin proteins in formalin-fixed, paraffin-embedded tissues of a variety of tumors (squamous cell carcinomas, adenocarcinomas, mesotheliomas, and transitional cell carcinomas) was evaluated. Three types of trypsin (Type II and Type IX porcine trypsin and Type III bovine trypsin) and varying concentrations of trypsin were assessed. Immunoreactivity of keratin proteins was determined using rabbit anti-keratin antibodies and monoclonal antibodies (combination of AE1 and AE3) and immunoperoxidase techniques. Preliminary trypsinization was mandatory for optimal immunoreactivity of keratin proteins using either polyclonal or monoclonal antibodies. Excellent results were obtained using Type II porcine trypsin at concentrations of 25 mg/dl for 30-45 min or 50 mg/dl for 20 min, at 37 degrees C. Trypsin treatment with excessive concentrations of enzyme and/or extended incubation times promoted tissue digestion and in some cases, yielded decreased immunoreactivity and altered staining patterns.     

Relationship of CA 125 and CA 19.9 with lung carcinoma histological subtype: preliminary study

The aim of this work was to study the possible utility of simultaneous determination of CA 125 and CA 19.9 in patients with lung cancer. Serum levels of both markers were studied in 87 patients without metastases (Mo), 72 patients with distant metastases (MT) and 15 cases without clinical evidence of disease after primary treatment (NED). Sixty-five tumors were epidermoid, 34 were adenocarcinomas, 24 were cell undifferentiated carcinomas and 51 were small-cell carcinomas. Sera from 75 healthy subjects and 20 patients with benign lung disease were used as controls. The cut-off values used were 35 and 37 U/ml for CA 125 and CA 19.9, respectively. CA 125 and CA 19.9 serum levels were within normal limits in all control patients. In NED patients these markers were not elevated, except in one with chronic liver disease who showed elevated CA 19.9 (76 U/ml). Twenty-five percent of Mo lung cancer patients and 40.3% of MT cases had CA 19.9 over 37 U/ml. Abnormally high levels of CA 125 were found in 18.7% and 22.9% of Mo and MT patients, respectively. Sixty percent of patients with large cell undifferentiated carcinoma had elevated CA 125 (mean 176 U/ml) compared to 15.4% of patients with all other histological types of tumors combined (54.3 U/ml, p less than 0.01). CA 19.9 serum levels were also more often elevated in patients with large cell undifferentiated carcinomas (50%, 7/14 cases) than in other histological types (30%, 36/120 patients), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of a panel of monoclonal antibodies in ultrastructurally characterized small cell carcinomas of the lung

In recent electron microscopic studies of 51 small cell carcinomas of the lung, the ultrastructural features of epithelial differentiation, particularly the presence of desmosomes, were associated with a tendency toward localized disease, clinical resectability and relatively long survival. Thirty-three of these cases were studied with a panel of monoclonal antibodies (B72.3, B1.1, AE1-AE3 and anti-Leu-7) directed against tumor-associated glycoprotein (TAG-72), carcinoembryonic antigen (CEA), cytokeratin and Leu-7 (an antigen common to natural killer cells and small cell lung carcinomas) to assess the correlation between the immunocytochemical and ultrastructural evidence of differentiation in tumors lacking differentiation at the light microscopic level. Of four small cell carcinomas with ultrastructural glandular differentiation, two were positive for CEA, three were positive for cytokeratin, and none were positive for TAG-72 and Leu-7. Of six tumors with ultrastructural squamous features, cytokeratin was expressed by three, CEA by one and TAG-72 and Leu-7 by none. Of the 23 classic oat cell carcinomas, cytokeratin was expressed by 14, Leu-7 by 3, CEA by 1 and TAG-72 by none. While the pattern of antigen expression did not predictably reflect the submicroscopic features, there was a significant association between keratin staining and extent of disease. The prospective use of similar antibody panels with both cellular and histologic material may therefore help to define clinically relevant categories of this biologically heterogeneous neoplasm.     

Distinction between carcinoma cells and mesothelial cells in serous effusions. Usefulness of immunohistochemistry

The usefulness of an immunoperoxidase battery to distinguish carcinomatous from benign effusions was examined. Cell block sections from 90 previously diagnosed effusions were stained with antibodies to Leu-M1, B72.3, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and vimentin. The 90 cases comprised 69 carcinomas (23 mammary, 16 ovarian, 10 pulmonary, 7 gastrointestinal [GI] and 13 others), 2 malignant mesotheliomas and 19 cases with reactive mesothelial cells only. EMA and vimentin were the most useful markers for distinguishing carcinoma cells from reactive mesothelial cells. EMA reacted with 86% of the carcinomas while vimentin reacted with 90% of the reactive cases. Leu-M1, B72.3 and CEA, although generally less sensitive than EMA, were also helpful in this regard. Additionally, the use of Leu-M1 and CEA together may help to distinguish pulmonary from GI carcinomas.     

Somatostatin receptor imaging in the diagnosis and treatment of neuroendocrine tumors.

Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radioactive isotope-labelled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 30/31 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, 5/7 small cell lung cancers, 6/7 neuroblastomas, 38/49 primary breast cancers, and 0/18 pancreatic adenocarcinomas. Also 11/11 meningiomas, 4/4 astrocytomas and 0/3 glioblastomas could be visualized. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It is an in vivo method for the recognition of neuroendocrine cancers. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers.     

Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas

We studied the expression of villin, a microfilament-associated, actin-binding protein typical of brush-border microvilli, in a variety of human carcinomas by applying immunofluorescence microscopy to frozen sections and immunoblotting methods to tissue extracts using a rabbit antiserum and a monoclonal antibody specific for villin. All of the 24 primary and metastatic colorectal adenocarcinomas tested were uniformly and strongly positive for villin, with the immunocytochemical labeling concentrated at the luminal cell margin. In poorly differentiated tumor areas, rudimentary tubules were stained. All of the six tubular adenocarcinomas of the stomach studied as well as two adenocarcinomas of the gall bladder and a hepatocellular carcinoma were also villin-positive. Villin was detectable in 12 of 14 adenocarcinomas of the pancreas; in some of these cases, its distribution was heterogeneous. Among 21 renal cell carcinomas investigated, positivity for villin was seen in nine of 13 clear cell tumors (especially those of grade II), and in all four chromophilic cell tumors; however, all four chromophobe cell tumors studied were negative. Four of 11 endometrial but none of nine ovarian carcinomas were (uniformly or focally) villin positive. Of 18 adenocarcinomas of the lung studied, one was uniformly and four focally positive for villin, while the remainder were negative. All of the other epithelial tumors studied, including 12 adenocarcinomas of the breast and seven epithelial or biphasic pleural mesotheliomas, were villin negative. Our results show that the expression of villin in intestinal epithelial cells is consistently maintained in their corresponding carcinomas, even when the organized brush-border structure has been lost. The presence of villin in some endometrial and pulmonary adenocarcinomas--in contrast to its absence in the respective normal epithelia--suggests that this protein is newly expressed during hyperplasia, dysplasia, or carcinogenesis. Determining the presence or absence of villin and its immunocytochemical staining pattern in metastatic adenocarcinomas may be of some help in determining the type and site of the primary tumor.     

Comparative biological properties of a recombinant chimeric anti-carcinoma mAb and a recombinant aglycosylated variant

Summary It has been demonstrated previously that the degree of glycosylation of a molecule may alter its pharmacokinetic properties and, in the case of an antibody, its metabolism and other biological properties. Transfectomas producing aglycosylated chimeric B72.3(1) pancarcinoma monoclonal antibody (mAb) were developed by introduction of the eukaryotic expression construct pECMgpB72.3 HuG1-agly, into SP2/0 murine myeloma cells producing the chimeric chain of mAb B72.3. After cell cloning, one subclone with the highest binding to the TAG-72-positive human colon carcinoma was designated mAb aGcB72.3, and its biological and biochemical properties were compared with those of the chimeric B72.3(1), designated mAb cB72.3. Polyacrylamide gel electrophoresis showed that under non-reducing conditions, the molecular masses of the aGcB72.3 and cB72.3 mAbs were 162 kDa and 166 kDa respectively. The heavy chain of mAb aGcB72.3 had a slightly faster mobility than that of cB72.3, while the mobility of the light chains of the two chimeric mAbs was similar. No difference was observed in the isoelectric points of either chimeric mAb. Liquid competition radioimmunoassays demonstrated that the aGcB72.3 and cB72.3 mAbs have comparable binding properties to TAG-72. These studies demonstrate that aglycosylation of the chimeric IgG1 mAb B72.3 at theCh2 domain, as has been shown for other mAbs [Dorai H., Mueller B., Reisfeld R. A., Gillies S. D. (1991) Hybridoma 10:211; Morrison S. L., Oi V. T. (1989) Adv Immunol 44:65], eliminates antibody-dependent cell-mediated cytotoxicity activity, but does not substantially alter affinity or plasma clearance in mice. These studies also demonstrate for the first time (a) no difference in plasma clearance of an aglycosylated and a chimeric mAb in a primate after i.v. inoculation; (b) a difference (P 0.05) in mice in the more rapid peritoneal clearance of a chimeric mAb versus an aglycosylated chimeric mAb; (c) higher (0.05 P 0.1) tumor:liver ratios at 24, 72 and 168 h using¹¹¹In-labeled aglycosylated chimeric mAb versus chimeric mAb. Since the liver is the major site of metastatic spread for most carcinomas, slight differences in tumor to normal liver ratios may be important in diagnostic applications. These studies thus indicate that comparative analyses of a novel recombinant construct (i.e., aglycosylated) and its standard chimeric counterpart require documentation in more than one system and are necessary if one is ultimately to define optimal recombinant/chimeric constructs for diagnosis and therapy in humans.     

Fine needle aspiration cytology of atypical carcinoid of the lung

The cytologic features of eight atypical carcinoid tumors of the lung, as observed in fine needle aspiration (FNA) specimens, are described in detail. They were compared with 21 pulmonary squamous-cell carcinomas, 16 adenocarcinomas, 5 small-cell undifferentiated carcinomas, 3 large-cell undifferentiated carcinomas and 1 typical carcinoid tumor. Atypical carcinoid tumor was easily distinguished from the other pulmonary neoplasms in most instances. Only two poorly differentiated squamous-cell carcinomas (one of which had atypical carcinoid as a component) and one small-cell undifferentiated carcinoma had similar cytologic features. One atypical carcinoid also had cytologic features similar to small-cell undifferentiated carcinoma. Because atypical carcinoid and small-cell undifferentiated carcinoma, at times, may be difficult to separate in FNA specimens, surgical resection of all stage I neoplasms with cytologic features evocative of either neoplasm is recommended.     

Flow cytometric analysis of human lung cancer. Correlation with histologic type and stage

DNA ploidy and cell-cycle characteristics of 65 operable lung cancers (41 adenocarcinomas, 19 epidermoid carcinomas, 3 large-cell carcinomas and 2 small-cell carcinomas) were analyzed using flow cytometry. Eighty percent of the tumors were aneuploid. The mean DNA index was lower in epidermoid than in adenocarcinoma. In adenocarcinoma, a low DNA index was correlated with early-stage disease; no correlation between DNA index and stage was observed in the other cell types. The %S-phase cells was highest in two cases of undifferentiated large-cell carcinoma and lowest in adenocarcinoma. The RNA index was increased approximately two-fold in all cell types. Longer follow-ups will be required to establish any correlation between the cell kinetic measurements reported here and survival times.     

The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.