Integrins and laminins in human renal carcinoma cells and tumors grown in nude mice.

We studied by indirect immunofluorescence microscopy the distribution of integrins and laminins in four human renal cell carcinoma cell lines (CAKI-2, A498, CAKI-1, and ACHN) in vitro and in s.c. xenografts in nude mice. In vitro, all four cell lines expressed the alpha 1, alpha 3, alpha v, beta 1, beta 3, and beta 5 subunits and three expressed the alpha 6 subunit; all cell lines expressed laminin A, B1, and B2 chains. Histologically, the CAKI-2 and A498 cells formed differentiated grade 1 (G1) and G2 tumors, respectively, while the CAKI-1 and ACHN cells formed poorly differentiated G3 tumors. The described integrin profile was largely retained upon xenografting. Basal polarization of the alpha 3 and alpha 6 integrin subunits was found in the differentiated tumors, and human laminins were detected as discrete linear structures surrounding tumor cell clusters in these tumors, suggesting that the cells have retained a polarized cell-laminin interaction characteristic of normal tubular epithelial cells. A disorganized distribution of integrins and laminins was noted in the G3 tumors. We conclude that these renal carcinoma cell lines displayed an integrin repertoire similar to that of clinical renal carcinomas and retained it upon xenografting. Furthermore, the organization of integrins and laminins in the xenografts correlated with histological grade.

Monoclonal antibody 44-3A6 as a probe for a novel antigen found on human lung carcinomas with glandular differentiation.

This paper describes an immunoglobulin G1 mouse monoclonal antibody (MCA) 44-3A6 directed against a human adenocarcinoma of the lung, cell line A549. This hybrid is a fusion product of the mouse myeloma SP 2/0.Ag14 and spleen cells from a BALB/c mouse which had been hyperimmunized with A549. Live cell radioimmunoassays, immunofluorescences, and fluorescent activated cell sorter analysis indicate that MCA 44-3A6 reacts with a cell surface antigen. Western blot analysis identifies a major antigen band with the apparent molecular weight of 40,000. Enzyme treatment of A549 target plates shows that the antigen is sensitive to proteases. This MCA does not react with carcinoembryonic antigen. Patients having a variety of different lung carcinomas do not appear to have detectable antigen in their serum, nor does the antigen appear to be shed into culture supernatants by human lung carcinoma cell lines. The antigen is preserved in formalin-fixed, paraffin-embedded tissue sections and shows a cell surface and/or cytoplasmic staining pattern. Immunohistochemical staining of various bronchopulmonary carcinomas demonstrated binding to be restricted to tumors with features of "glandular" differentiation. This MCA may have clinical and diagnostic utility due to its selective binding for a subset of carcinomas of the lung.

Immunohistochemical analysis of human pulmonary carcinomas using monoclonal antibody 44-3A6.

A monoclonal antibody, 44-3A6, was raised against the human pulmonary adenocarcinoma cell line A549. This antibody recognizes a protein antigen at the cell surface, which is preserved after formalin fixation and paraffin embedding. Immunohistochemical staining of lung tissue with this antibody revealed diffuse immunoreactivity of type II pneumocytes. Bronchial epithelial cells were also focally immunoreactive. Immunostaining of various bronchopulmonary carcinomas demonstrated characteristic patterns of reactivity. All of the 42 adenocarcinomas and 18 carcinoids were strongly immunoreactive either diffusely or focally. The immunoreaction occurred at the cell membrane and/or in the cytoplasm. None of the 39 squamous cell carcinomas, 12 bronchioloalveolar carcinomas, and 30 small cell neuroendocrine carcinomas was immunostained. Ten intermediate cell neuroendocrine carcinomas and 8 well-differentiated neuroendocrine carcinomas were relatively weakly immunoreactive, while 7 and 2 of them were negative. Six adenosquamous carcinomas were focally positive in glandular and "basaloid" areas, whereas squamous areas were negative. Twenty-one large cell carcinomas were focally immunoreactive, while 6 were negative. It appears that MCA 44-3A6 is an effective marker for certain features of "glandular" differentiation, which may be present even in tumors lacking obvious glands, and that it may be useful for the differential diagnosis of various bronchopulmonary carcinomas.

Malignant cells of epithelial phenotype limited to thoracic lymph nodes.

Asymptomatic thoracic lymphadenopathy was incidentally discovered in three patients with no definitive diagnoses. Enlarged lymph nodes, removed at thoracotomy, had irregularly distributed, pleomorphic, malignant-appearing cells. Mitoses were frequent. Electron microscopy showed tonofilament bundles and desmosomes. By immunocytochemistry, these cells uniformly expressed desmoplakin and cytokeratins 8 and 18 and various patterns of coexpression with other cytokeratins. One patient had lymphadenectomy, segmental lung resection and radiotherapy; the second had lymphadenectomy and later a lymphadenectomy with pneumonectomy; and the third had lymphadenectomy and radiotherapy. Neoplastic cells were detected exclusively within thoracic lymph nodes. The patients are well 111, 39 and 13 months after initial presentation. The clinical course and the patterns of intranodal distribution and marker expression of the neoplastic cells are unusual and distinct from most carcinomas metastatic to lymph nodes and reminiscent of "lymphoepithelioma-like carcinomas" described in the thymus and other sites. While the malignant cells may reflect metastases from as yet occult primaries or malignantly transformed ectopic epithelial nests, these tumours may arise by transformation from the cytokeratin-positive "extrafollicular reticulum cells" indigenous to lymphoid organs.

Neuroendocrine carcinomas of the colon. Ultrastructural and biochemical evidence of their secretory function.

Four cases of malignant colonic tumors diagnosed by light microscopy as "small cell undifferentiated carcinomas" were shown by electron microscopy to have neurosecretory-type granules. Biochemical analysis of tumor tissue extracts disclosed the presence of considerable levels of VMA and catecholamines in all tumors; 5-HIAA was present in one tumor. Clinically, there had been no signs or symptoms attributable to those or related substances. Similar observations have been reported in a variety of neuroendocrine neoplasms; for example, the demonstration of neurosecretory-type granules and determination of amine or peptide materials in tumor tissue or body fluids may not be necessarily reflected in clinical hormonal syndromes or obvious metabolic abnormalities. Our structural and biochemical observations indicate that, regardless of clinically evident hormonal activity or lack thereof, some small cell "undifferentiated" colonic cancers derive from APUD elements, and therefore they should be classified within the group of neuroendocrine carcinomas. The evident secretory capabilities of these carcinomas suggest obvious diagnostic possibilities and could conceivably lead to a reappraisal of current therapy.

Stability of the glycoprotein A-80 in prostatic carcinoma subsequent to androgen deprivation therapy.

Androgen deprivation therapy (ADT) results in profound morphologic changes in the benign and malignant prostatic epithelium, including acinar shrinkage and distortion, cytoplasmic clearing, and nuclear hyperchromatism. Data on the immunophenotype of prostatic carcinoma following ADT are limited. A-80 is an oncodevelopmental, mucinous glycoprotein that is strongly and consistently upregulated in high-grade prostatic intraepithelial neoplasia and adenocarcinoma; its expression following ADT has not been investigated. We applied a monoclonal antibody to A-80 to paraffin sections of 54 prostatic carcinomas surgically removed after ADT (Leupron with or without flutamide) and found immunoreactions in 53 of 54 samples (98%). Intense staining was seen in cancer glands, solid aggregates, single cells, and mucinous pools as well as in poorly defined acini lined by shrunken and distorted cells that were difficult to identify as malignant. Hemangiopericytoma-like areas showed A-80 staining in the lumina. Normal, metaplastic, hyperplastic, and atrophic ducts were not similarly reactive. Our findings indicate that there is remarkable stability of the upregulated A-80 glycoprotein in prostatic adenocarcinoma after ADT, despite severe architectural and cytologic alterations. The A-80-reactive colloid pools may reflect ruptured neoplastic glands and spillage of secreted material into stromal spaces. Strong A-80 staining, combined with sporadic cytokeratin reactions in the lumina of hemagiopericytomatous areas, suggests that these are souvenirs of carcinomatous glands revealed by antigenic relics of their component cells. The persistence of A-80 immunoreactivity provides a useful marker for recognizing and monitoring prostatic carcinoma after ADT.

The spectrum of olfactory neural tumors. A light-microscopic immunohistochemical and ultrastructural analysis.

Twenty-eight malignant olfactory neural tumors representative of the histologic spectrum commonly designated as olfactory neuroblastoma were subdivided into two groups: Group I closely resembling classical neuroblastoma (20 cases), and Group II exhibiting neuroendocrine features (eight cases). Immunohistochemically, the tumors were analyzed by using antibodies to keratin, neurofilament protein, S-100, and neuron specific enolase. Neuron specific enolase was the most consistently positive in both groups. Single S-100 positive cells, within or at the edges of tumor nests, often corresponded ultrastructurally to Schwann cells at the tumor-stroma interface. Keratin and neurofilament proteins were expressed singly or together by a small number of cases in both groups. All 11 tumors examined ultrastructurally exhibited neuronal processes containing dense-core granules. The results indicate the following: (a) the reliable diagnostic utility of electron microscopy; (b) the frequent occurrence of Schwann cells in these tumors despite their inconspicuousness by light microscopy; and (c) the unexpected expression of keratin by tumors in both groups. The single or coexpression of keratin-neurofilament protein may define a subset of these tumors for which the clinical significance is presently unclear.

Synaptophysin. A new marker for pancreatic neuroendocrine tumors.

Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.

Neuroendocrine skin carcinoma associated with calcitonin production: a Merkel cell carcinoma?

An elderly woman presented with an ulcerating skin carcinoma located over the right parietal area. It healed after local radiotherapy but recurred locally and metastasized to the subcutaneous tissue and one regional lymph node. Neurosecretory granules were demonstrated ultrastructurally, and blood levels of calcitonin were repeatedly elevated. A metastasizing medullary carcinoma of the thyroid was suspected, and a total thyroidectomy was performed; however, no medullary carcinoma or C cell hyperplasia could be identified. Furthermore, the calcitonin levels remained unchanged following thyroidectomy, whereas they decreased twice after the skin tumor or its metastases were ablated. Clinical follow-up for over seven years revealed no other lesion that could have been responsible for the overproduction of calcitonin. The ultrastructural features of this skin carcinoma and its metastases, particularly the neurosecretory granules, were reminiscent of those of the so-called Merkel cell. We conclude that this skin carcinoma might indeed produce calcitonin, that this tumor may be derived from Merkel cells, and that Merkel cells may belong within the APUD system.

Malignant gastric neuroendogrinomas. Ultrastructural and biochemical characterization of their secretory activity.

In two cases of malignant gastric tumors originally diagnosed as undifferentiated carcinomas electron microscopy revealed a neurosecretory type of granule. Subsequently tumor extracts were tested by biochemical methods and shown to have vanillylmandelic acid and 5-hydroxy-3-indoleacetic acid activity. Neither patient had signs or symptoms referable to the presence of these or related substances. These observations parallel those made in a variety of neuroendocrine tumors in which demonstration of neurosecretory granules or isolation of amine or peptide materials or their metabolites has not necessarily been reflected in clinical hormonal syndromes. Our findings indicate that regardless of clinically apparent hormonal activity or lack thereof, some undifferentiated gastric carcinomas may in fact derive from neuroendocrine APUD elements.

Ultrastructural and biochemical analysis of "undifferentiated" pulmonary carcinomas.

Seven cases of "undifferentiated" pulmonary carcinoma were studied ultrastructurally; five were of the typical oat cell variety and the remaining two consisted of larger cells. In three of the former and both of the latter cases neurosecretory-like granules were demonstrated. Biochemical analysis of tumor tissue extracts revealed 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in all instances. No hormonal syndrome or metabolic abnormality was detected in any of the patients. The concomitant morphologic demonstration of neurosecretory-like granules and the presence of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamines in neoplastic tissue would provide further evidence that these tumors may indeed arise from bronchial endocrine cells and could therefore be classified within the group of neuroendocrine carcinomas. Also it seems apparent that these neuroendocrine bronchial carcinomas may include tumors consisting of cells somewhat larger than the typical oat cell. The observation of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in two oat cell carcinomas in which neurosecretory granules could not be demonstrated poses an interesting problem whose solution may only derive from further studies.

"Myeloma lung"--a previously unreported complication of multiple myeloma.

A 52-year-old man with known lambda light-chain multiple myeloma developed chronic renal failure, which was proven by renal biopsy to be the result of "myeloma kidney." Terminally, disseminated pulmonary infiltrates developed. Postmortem examination showed the infiltrates to consist of neoplastic plasma cells with crystalline casts, strikingly similar to those found in the kidneys. The term "myeloma lung" is proposed to describe this unusual and heretofore unreported complication of multiple myeloma.

The fine structure of human thyroid cancer.

This ultrastructural description of human thyroid cancers is based on the available literature and on our own studies of about 150 cases. Electron microscopy is an invaluable diagnostic adjunct to light microscopy, as it may eliminate inaccurate designations such as "small cell malignant tumors of the thyroid," which include tumors of different histogenetic origin with a different prognosis and treatment that share only a similarity in appearance under the light microscope. Ultrastructure is also of diagnostic importance in cases of medullary carcinoma that imitate papillary or follicular patterns or lack amyloid stroma. Its importance in separating follicular adenomas from carcinomas, however, has not been proven. In conjunction with other methods ultrastructural study might throw new light on the controversial classification of papillary and follicular carcinomas and improve our understanding of their different biologic behavior. Immunoelectron microscopy may help in solving the problem of amyloid pathogenesis in endocrine tumors and in charting the subcellular mechanisms involved in the production of multiple polypeptide hormones in a single tumor.

Immunolocalization of integrins in the normal lung and in pulmonary carcinomas.

Cryosections of normal adult lung (n = 7) and pulmonary epithelial tumors, including squamous (n = 8), adeno (n = 8), bronchioloalveolar (n = 5), and large cell (n = 4) carcinomas (SCC, ACC, BAC, LCC), carcinoids (Cd, n = 7), and neuroendocrine carcinomas (NEC) of variable grades (n = 14) were immunostained by the avidin-biotin peroxidase (ABC) method with monoclonal antibodies to the alpha1-6 and alpha(v) and the beta1-4 integrin subunits. Normal adult alveolar septae showed variably intense immunoreactivity for alpha1,3,6 and beta1, whereas reactions for alpha5 and alpha(v) were weaker and uneven; the remaining integrin subunits were not detected. Bronchial and bronchiolar epithelium showed variably intense staining for alpha2.3,6,v and beta1,4. Reactions were often, though not invariably, basally polarized. SCC, ADC, and LCC showed variably intense reactions for alpha2.3,6,v and beta1,4. BAC were strongly and uniformly stained for alpha1.3 and beta1. In Cd, alpha1,2,3,v and beta1 reactions were noted, whereas in NEC, weak alpha1,3 and beta1 staining was detected with only traces of alpha6 and alpha(v). We conclude that alveolar epithelial cells do not express the hemidesmosome-associated, laminin-binding integrin alpha6beta4 of the bronchial epithelium but rather the alpha1beta1 and alpha3beta1, collagen IV, and laminin receptors, respectively. SCC, ADC, and sampled LCC express an integrin repertory qualitatively similar to that of the bronchial epithelium. Distinct from the latter, the integrin repertory of BAC parallels that of the alveolar epithelium by its strong expression of the multipotential alpha1beta1 and alpha3beta1 integrins. NEC tumors do not display the laminin receptors alpha6beta4 and alpha6beta1 shown by SCC and ADC but express instead alpha1beta1, a collagen IV-laminin receptor rarely found in epithelial neoplasms except for BAC. In NEC tumors, integrins, especially alpha2, decrease with dedifferentiation. Notably distinct from epithelial mesotheliomas, the major fibronectin-binding integrin alpha5beta1 was not found in any type of lung carcinoma.

Intracytoplasmic lumina in bladder carcinomas.

Intracytoplasmic lumina were identified in neoplastic cells from four human and three canine "spontaneous" bladder carcinomas. They were also found in N-[4-(5-nitro-2-furyl)-2-thiazoly] formamide induced bladder carcinomas in rats as well as in cultured tumor cell lines derived from these experimental tumors. Intracytoplasmic lumina were readily recognized in 5 micrometer. paraffin embedded and 1 micrometer. epoxy embedded sections. Histochemically, intracytoplasmic lumina were strongly positive with PAS and alcian blue-PAS; mucicarmine stain was positive as unevenly distributed droplets. Ultrastructurally lumina were defined by a symmetric unit membrane; they displayed abundant pleomorphic microvilli, which contained prominent cytoskeletal elements. Step section electron microscopic study revealed continuity between intracytoplasmic lumina and the extracellular space in only one case of experimental bladder carcinoma; otherwise they appeared to be entirely encompassed within the cytoplasm. No instance of exocytosis in relation to intracytoplasmic lumina was found. Our observations suggest that intracytoplasmic lumina may be rather frequent in several forms of urothelial carcinoma. They appear to be predominantly but not invariably intracytoplasmic. The mechanism that may determine the development of continuity between intracytoplasmic lumina and the extracellular space and the adduced relationship between intracytoplasmic lumina and the process of secretion remain undetermined.

Immunolocalization of glycoprotein A-80 in prostatic carcinoma and prostatic intraepithelial neoplasia.

A-80 is a mucin-like glycoprotein associated with exocrine differentiation that shows little or no expression in normal exocrine cells and typical adenomas, but is upregulated in dysplasia and adenocarcinoma of certain organs. Its expression has not been systematically examined in prostatic adenocarcinoma and its putative precursor, prostatic intraepithelial neoplasia (PIN). The authors applied a mouse monoclonal antibody against A-80 in paraffin-embedded sections from 103 cases of prostatic carcinoma, 26 cases of nodular hyperplasia, 7 autopsy samples from normal young adult prostates, and 12 fetal prostates. All but one cancer reacted, although expression was heterogeneous; 75 of 103 stained extensively (> 3+ on a 0 to 5+ scale) and strongly. Staining extent and intensity were independent of tumor grade, and tended to be strong even when focal. Seventy-seven of 84 foci (92%) of high-grade PIN and 38 of 52 foci (73%) of low-grade PIN stained for A-80; reactions were most extensive and intense in high grade PIN. Only 5 of 26 cases (19%) of hyperplasia reacted, and this consisted of weak to moderate staining in sporadic cells; the remainder were negative. Normal adult prostatic epithelium did not express A-80 except for weak and inconsistent staining in foci of inflammation and infarction; atrophic glands were negative. Fetal prostate showed focally strong reactivity. These results indicate that A-80 is selectively expressed in most cases of intraepithelial neoplasia and prostate cancer, but is usually absent in benign and hyperplastic epithelium. The upregulation of glycoprotein A-80 in PIN and adenocarcinoma parallels observations in other organs, such as the breast and colon, suggesting that this is a significant oncodevelopmental molecule with potential clinical applications.

Vitronectin in the cirrhotic liver: an immunomarker of mature fibrosis.

Vitronectin (Vn) is a multifunctional plasma glycoprotein produced by hepatocytes. Vn has been studied extensively as a cell adhesion molecule. However, its localization in the hepatic extracellular matrix has received relatively little attention. Cryosections of 5 normal liver samples and of 20 specimens showing posthepatitic cirrhosis were stained by the avidin-biotin complex method with a well-characterized monoclonal antibody to Vn. The extent and intensity of immunostaining were assessed semiquantitatively (0, no staining; 1+, weak focal staining; 2+, strong focal staining; 3+, strong diffuse staining). Paraffin sections from the same samples were stained with Masson trichrome (MT) and Shikata orcein (Or) methods. Frozen samples from selected cases were analyzed by Western blotting. In the normal liver, 3+ staining was limited to portal vessels. The portal tract connective tissue showed minimal staining (0 to 1+). Cirrhotic septa showed strong staining (2+). Septa lacking significant inflammation and composed of dense connective tissue, as indicated by MT and Or stains, showed the strongest Vn reactions (3+). Immunoblotting data strongly correlated with Vn increase in cirrhotic livers. Vn immunoreactivity is markedly increased in the cirrhotic liver matrix, regardless of the documented decrease in plasma Vn. Binding to collagen, elastin, and proteoglycans is the current favored mechanism of Vn deposition in tissues. Previous studies in cirrhotic patients showed increased affinity of plasma Vn to collagen. Vn is also increased in aged skin, associated with dermal elastic fibers. In other tissues, Vn deposition reflects chronicity of injury. Therefore, Vn immunoreactivity in liver can be considered a marker of fibrosis, especially of chronic/mature fibrosis, paralleling previous observations on enhanced orcein staining of cirrhotic septa. Immunolabeling of biopsy specimens with Vn and tenascin, a marker of ongoing remodeling or recently formed fibrous tissue, could be diagnostically helpful.

Pleural mesotheliomas have an integrin profile distinct from visceral carcinomas.

Cryosections of epithelial, sarcomatoid, and biphasic malignant mesotheliomas (EMM, n = 11; SMM, n = 5; BMM, n = 6) of the pleura were immunostained with monoclonal antibodies to integrin subunits alpha 1-6 and v, and beta 1-4. Localization patterns were compared with those known to occur in pulmonary and other adenocarcinomas (PADC, ADC). EMM and the epithelial component of BMM (ecBMM) expressed alpha 1,3,5,6, and v and beta 1 and 4. SMM and the sarcomatoid elements of BMM (scBMM) reacted variably for alpha 1,3,5,6 and v, and beta1. Reactions for alpha3, found in all tumors, were strongest in EMM, ecBMM, and PADC. Our findings indicate that EMM and ecBMM parallel PADC and most ADC in their expression of alpha6 beta4, underscoring that this laminin integrin receptor is intimately associated with these neoplastic epithelial phenotypes. Also, our observations on alpha3 beta1 suggest that this cell-cell adhesion-mediating integrin is related to the epithelial phenotype. Notably, all malignant mesotheliomas (MM), including those with distinct glandular structures, expressed the alpha5 beta1 fibronectin receptor, thus paralleling most sarcomas and differing from PADC and most other ADC. We conclude that irrespective of architectural and cytologic variants, transformed mesothelial cells possess an integrin repertory that differs significantly from that of most ADC, including those of the lung. These findings set mesothelium apart from epithelia and may prove helpful as adjunct tools for the differential diagnosis between EMM and AD.

Demonstrability of the glycoprotein A-80 in postradiation prostatic carcinoma.

Radiation therapy results in significant morphological changes in prostatic carcinoma, including decreased cancer size, acinar shrinkage and distortion, cytoplasmic vacuolization, and nuclear pyknosis. Benign acini usually display enlarged, atypical cells with hyperchromatic nuclei. These changes confound the evaluation of limited postradiation samples. The glycoprotein A-80 is known to be upregulated in prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma. In this study, we assessed the expression of A-80 in radiation-treated prostatic carcinoma. Paraffin sections from 64 postradiation prostatic carcinomas obtained at salvage prostatectomy were immunostained with a monoclonal antibody to A-80; selected sections were doubly immunostained with antibodies to A-80 and various cytokeratin polypeptides. All cases showed readily detectable and often intense staining in the cytoplasm of cancer cells and in intraluminal material of malignant acini. The extent and intensity of the reactions were independent of cancer size and grade. Strong reactions were seen in preserved and distorted acini, clear cell areas, single cancer cells, and in colloid pools with few or no recognizable cancer cells. PIN was present in 34 cases (53%), of which 27 (79%) stained strongly for A-80; atrophic and hyperplastic acini generally did not stain, irrespective of the degree of cellular atypia. The A-80 glycoprotein appears remarkably durable and is readily demonstrable in postradiation prostatic carcinoma despite profound architectural and cytologic changes. This characteristic may prove useful in evaluating small samples for confirmation of diagnosis and determination of extent of residual or recurrent prostatic carcinoma after radiation therapy.

Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis.

Intravascular Lymphomatosis (IL) is a rare and usually aggressive form of non-Hodgkin's lymphoma characterized by the growth of neoplastic cells within vascular lumina that usually presents with skin or central nervous system (CNS) involvement. The mechanism(s) for the selective intravascular growth of this neoplasm remain(s) unexplained. We now report clinical and immunohistologic data on surgical material from 6 cases of IL; in 4 of 6 cases, autopsies were performed. Our IL cases shared the following features: (1) B-cell lineage; (2) lack of skin involvement at presentation; (3) aggressive behavior; and (4) lack of extravascular lymphomatous masses; in addition, 1 case had an associated gastric low-grade MALT lymphoma. We studied by immunohistochemistry formalin-fixed, paraffin-embedded sections with monoclonal antibodies to molecules known to be involved in lymphocyte and endothelial adhesion phenomena, that is, CD29 (beta1 integrin subunit), CD43 (leukosialin), CD44 (H-CAM), CD54 (ICAM-1), embryonal N-CAM (e-NCAM), and EMA (episialin). In all cases, the surfaces of IL aggregates reacted for CD44 but were consistently negative for CD29; also absent was CD54. Conversely, the integrity of the endothelial cells was underscored by their even reactivity for CD29, CD44, and CD54. Given that CD29 is currently regarded as critical for lymphocyte trafficking in general and for transvascular migration in particular, and CD54 is also involved in transvascular lymphocyte migration, we conclude that their consistent absence in IL may contribute to its intravascular and disseminated distribution pattern. The rather frequent association of IL with various conventional lymphomas is known; yet, one of our cases appears to be the first report of IL associated with a low-grade MALT lymphoma.