Adhesion molecules and tumor metastasis.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
V E Gould
Publications and source records attributed to V E Gould.
Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas.
The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha3 and alpha6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta1 and beta4 subunits, the beta1C splice variant of beta1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. All carcinomas expressed alpha3 extensively; alpha3 expression predominated (40 of 40) over alpha6 (25 of 40). In all alpha6-positive carcinomas, alpha6A was expressed, whereas alpha6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha3 and of the A or B intracytoplasmic domains of alpha6 were shown. Notably, in normal bronchial epithelium, alpha6 colocalized with beta4, whereas in the tumors, alpha6A frequently overlapped with beta1 in a circumferential pattern; alpha6beta1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta1C and Ki-67. The prevalence of alpha6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha6B prevails, and alpha6 predominates over alpha3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of alpha3 over alpha6 and of alpha6A over alpha6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.
Adenocarcinoma↗
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.
Adenocarcinoma↗
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.
Adenocarcinoma↗
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.
Androgen Antagonists↗
Differential diagnosis of small cell neuroendocrine carcinoma of the lung.
The clinical significance of a tumor classification rests in its usefulness to predict the natural history and response to therapeutic intervention of given tumor types. In this context, the importance of distinguishing between SCNC and neoplasms with which it has been confused is evident. In 1990, we re-evaluated a series of 50 patients who underwent a complete resection for tumors in which the diagnosis of small cell carcinoma was thought to have been established. Adjuvant therapy was given to nearly all patients, either pre- or postoperatively. We re-evaluated the histology of these tumors in light of the differential diagnosis described previously and correlated the diagnosis with the survival curves. We found that WDNC of any subtype has a much better prognosis than SCNC. Even locally advanced WDNC has a better prognosis than stage I completely resected SCNC (Fig. 9). Others have reported similar observations based on their own retrospective studies. Preliminary observations on completely resected chest wall PNETs suggest that these tumors also have a more favorable prognosis than SCNC. Given the difficulty in distinguishing SCNC from other tumors described previously, and the fact that most SCNC are treated without resection, the clinician should be familiar with certain features that are unusual for SCNC, and, therefore, suggest reconsideration of the diagnosis. In our patient population, SCNC is rarely seen in a lifetime nonsmoker and is distinctly unusual in an ex-smoker of 15 years of longer. T with chest wall invasion is a very unusual clinical stage for true SCNC. Small cell neuroendocrine carcinoma can invade the chest wall, but this is almost always in the presence of extensive mediastinal or distant metastases. Clinicians should also be wary of accepting the diagnosis of SCNC when serial radiographs suggest that the lesion is not growing or growing very slowly. Untreated SCNC usually demonstrates some growth over a 3-month period of observation. Finally, SCNC tends to be a chemosensitive neoplasm, at least initially. The occasional tumors that do not respond tend to enlarge and disseminate rapidly. If a tumor neither decreases nor increases in diameter over a 3-month period of presumably appropriate chemo- or radiotherapy, the diagnosis of SCNC should be questioned. Over the last 15 years, several reports have suggested a role for resection in the management of SCNC, especially for tumors diagnosed at an early stage. Other reports may have unwittingly exaggerated the long-term survival of SCNC treated by currently available chemo- and radiotherapy protocols. A careful re-evaluation of the diagnostic material in such cases may lead to more consistent results and the development of more rational therapeutic protocols.
Carcinoma, Small Cell↗
Tumor angiogenesis in pheochromocytomas and paragangliomas.
BACKGROUND: Angiogenesis correlates with growth and likely metastases in several tumors. To determine whether it has a similar role in pheochromocytomas, immunohistochemical staining of factor VIII was done on the tumor tissue of 42 patients. METHODS: Formalin-fixed, paraffin-embedded tissue was obtained from 29 women and 13 men with 24 primary adrenal and 18 extraadrenal pheochromocytomas. Patients were divided into two groups. Group 1 included 32 patients with benign pheochromocytomas, and group 2 included 10 patients with malignant tumors evidenced by capsular or vascular invasion (six), liver metastases (three), or periaortic lymph node metastases (one). Blood vessels highlighted by factor VIII staining of endothelial cells with labeled streptavidin-biotin were counted under light microscopy. Mean vessel count within a 10 mm2 micrometer disk was calculated under x100, x200, and x400 magnification fields. RESULTS: There were no significant differences in patient age or clinical symptoms between the groups. The mean tumor size in group 2 of 8.8 +/- 5.3 cm was larger than the mean of 4.8 +/- 2.8 cm in group 1 (p < 0.005). The mean counts of vessels in the x100, x200, and x400 magnification fields were 102 +/- 48, 40 +/- 18, and 19 +/- 9 in group 1, and 203 +/- 77, 73 +/- 28, and 37 +/- 15 in group 2. The number of blood vessels in group 2 was significantly higher than in group 1 (p < 0.001) in each studied field. CONCLUSIONS: In this study the number of tumor blood vessels correlated with the invasive behavior of pheochromocytomas. Tumor angiogenesis may be useful in determining the likelihood of malignant behavior in pheochromocytomas.
Adolescent↗
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.
Adult↗
Increased numbers of cytokeratin-positive interstitial reticulum cells (CIRC) in reactive, inflammatory and neoplastic lymphadenopathies: hyperplasia or induced expression?
A total of 291 enlarged lymph nodes showing a range of reactive-inflammatory processes, primary and metastatic neoplasms were studied to determine the distribution and immunoprofile of their cytokeratin-positive interstitial reticulum cells (CIRC) in comparison with normal nodes. In 258/291 nodes (89%), CIRC numbers were distinctly increased in the subcapsular, paracortical and, occasionally, in the medullary zones; often, these increased CIRC formed networks around follicles, sinuses and vessels. CIRC had comparatively small, irregularly shaped bodies and dendritic processes; occasionally, giant forms were noted. CIRC contained cytokeratins (CK) 8 and 18 but not 19, as shown by immunohistochemistry, and by gel electrophoresis with subsequent immunoblotting. They co-expressed vimentin consistently, alpha-smooth-muscle actin frequently, and desmin less frequently. They did not contain desmoplakins, Factor VIII, S-100, LCA, B and T lymphocyte- and macrophage-associated antigens, chromogranin A, synaptophysin or the A-80 glycoprotein. We found no clear correlation between the increased CIRC and given nodal disease processes. However, CIRC were most abundant in nodes free of but draining malignant tumours; bizarre CIRC assemblies were noted in HIV lymphadenopathy. CIRC appear to represent a subset of the so-called "fibroblastic reticulum cells" of lymph nodes. Their function remains undetermined; their increase in diverse lymphadenopathies suggests that they partake in nodal reactions to injury. It remains unclear whether the increase in CIRC relative number is due to proliferation or to CK gene induction processes but their presence and potential capability to undergo hyperplasia with dysplastic forms should alert pathologists to possible diagnostic pitfalls. In addition, we discuss that CIRC may undergo transformation and represent the "cell of origin" of certain CK-positive tumours restricted to lymph nodes.
Cytoskeletal Proteins↗
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.
Animals↗
Tenascin in inflammatory conditions and neoplasms of the urinary bladder.
Tenascin (Tn) is an extracellular matrix (ECM) glycoprotein strongly and widely expressed during embryogenesis. Tn is decreased in normal adult tissues but is reexpressed in numerous inflammatory, reparative and neoplastic processes. We immunostained samples of fetal and normal adult bladders and samples of bladder tissue from patients with chronic cystitis, detrusor hypertrophy, malakoplakia and transitional cell carcinomas (TCC) of all grades, with a monoclonal antibody (mAb) to Tn 143DB7. Sections of flat in situ carcinomas were also studied. In fetal bladders, strong and ragged Tn reactions were noted at the epithelial-stromal interface; in normal adult bladders, the reaction was delicate and less extensive. In chronic cystitis, Tn reactivity was enhanced particularly around prominent capillary blood vessels. In flat in situ carcinomas, Tn staining was stronger and more extensive than in normal mucosa but was often less extensive than in some examples of cystitis. In TCC I and II, Tn immunoreactivity was strong and predominated in the pericapillary stroma of the papillae; in infiltrating TCC II, comparatively limited Tn staining was noted. In deeply infiltrating grade III TCC with abundant stroma, Tn reaction was invariably strong and extensive, particularly around advancing tumor nests. The strongest Tn reactions were noted in invasive, high-grade TCC with abundant stroma. We conclude that in inflammatory-reactive processes, and in in situ carcinomas as well as in TCC, the extent and intensity of the Tn reaction correlates with the severity of the inflammatory infiltrate and with the extent of the stromal remodelling.
Adult↗
Immunolocalization of tenascin and cellular fibronectins in diverse glomerulopathies.
Frozen samples of minimal change glomerulopathy (MCG), and of membranous, segmental and diffuse lupus glomerulonephritis (MGN, SGN, DLGN) were studied to assess the distribution of tenascin (Ten), and the extradomains A and B (EDA- and EDB-) and oncofetal (Onc-) isoforms of cellular fibronectin (cFn). Cryosections were immunostained by the ABC method with specific monoclonal antibodies. In MCG, mesangial Ten and EDA-cFn reactions were increased. In MGN, mesangial Ten and EDA-cFn staining was enhanced except in segmental scars; convincing reactions were seen in cases with membranous transformation; spikes stained strongly. In SGN, variably intense staining for Ten and all cFn isoforms was seen in glomerular necrosis, proliferation and crescents; parietal epithelium EDA-cFn staining was noted. In DLGN, strong and extensive mesangial Ten and EDA-cFn staining was seen as were focal EDB- and Onc-cFn reactions. Parietal cells with and without crescents stained variably with all Mabs. Obsolete glomeruli were unreactive save for rare periglomerular Ten rims. Interstitial inflammation and fibrosis in MGN, SGN and DLGN had moderate to strong Ten and EDA-cFn staining with rare traces of EDB- and Onc-cFn. We conclude that enhanced Ten and EDA-cFn is a potentially reversible response to glomerular injury whereas the expression of EDB- and Onc-cFn apparently result from necrosis and/or cellular proliferation which lead to scarring. And, while mesangial cells are the major source of these molecules, epithelial cells might also partake in their synthesis.
Antibodies, Monoclonal↗
Immunolocalization of integrins in the normal and neoplastic colonic epithelium.
Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin. In NC, alpha 2 staining was strongest in crypt cells; alpha 1,3 and alpha v, and beta 1,3 and beta 4, and Ck 20 and villin predominated in superficial enterocytes. In TA and VA, monolayered glands showed integrin, Ck 20 and villin patterns that differed slightly from both crypt and superficial enterocytes. Complex glands in VA showed decreased integrin staining and basal polarization; Ck 20 and villin were strong only in luminal cells. CA showed overall weaker integrin staining than adenomas. Regardless of invasion depth, well formed malignant glands mimicked TA; pleomorphic glands mimicked VA with focal basal integrin polarization and solid clusters displayed scanty integrins, uneven Ck 20, and villin in occasional cells. Diverse integrins in crypt compared with superficial enterocytes reflect changing adhesive requirements as cells migrate and terminally differentiate. Decreasing expression and altered distribution of integrins, Ck 20 and villin noted in TA, VA, and in CA of increasing grade indicate that certain adhesive and cytoskeletal features more closely relate to glandular architecture than to depth of invasion.
Adenocarcinoma↗
Distribution of tenascin, cellular fibronectins and integrins in the normal, hyperplastic and neoplastic breast.
We present immunolocalization data on tenascin (Ten), and extradomains A and B (EDA-, EDB-) and oncofetal (Onc-) isoforms of cellular fibronectin (cFn), and alpha 1-6 and alpha v and beta 1-4 integrin subunits on cryosections of normal human breast, the spectrum of fibrocystic disease (FCD), and benign and malignant breast neoplasms. Fetal breast ducts were surrounded by broad Ten bands; adult breast ducts and acini were encompassed by thin continuous rims. In FCD, Ten was detectable and was clearly enhanced around hyperplastic ducts. Fibroadenomas showed uneven Ten periductal reactions while in all carcinomas, the stroma showed extensive and strong reactions that were most intense at the tumors' invasive edge. EDA-cFn's distribution was similar to Ten's but the staining was stronger while EDB- and Onc-cFn were virtually restricted to fetal breasts and carcinomas. In the normal adult breast, alpha 1,2,3 and alpha 6, and B1 and beta 4 integrins were detected in myoepithelial cells; weaker staining was also noted in the basolateral aspect of luminal cells; this profile was retained--and at times enhanced--in FCD, fibroadenomas and in situ carcinomas in which myoepithelial elements were present. In carcinomas, particularly in those of high grade, integrins tended to be reduced. However, mucinous carcinomas showed enhanced expression and the emergence of alpha 5 integrin that was not in the normal repertory; also a subset of infiltrating lobular carcinomas showed prominent alpha 1 and alpha 6 and beta 1 and--rarely--beta 4 staining distributed in delicate cytoplasmic processes (kinetopodia). These data indicate that the complex cell-matrix and cell-cell interactions of the normal breast are slightly altered in hyperplastic processes and benign neoplasms whereas profound chances occur in carcinomas. The latter display enhanced Ten and EDA- and Onc-cFn expression in particular, while most integrins appear decreased. Notably, mucinous and some lobular carcinomas display enhancement of certain integrins. The conspicuous localization of integrins in kinetopodia may be significant in relation to the invasive behavior of lobular carcinomas.
Breast↗
Neuroendocrine neoplasms of the lung. A 10 year perspective of their classification.
Based on clinical and pathologic data, neuroendocrine neoplasms of the bronchopulmonary tract may be classified into 3 groups: bronchial carcinoid; well differentiated neuroendocrine carcinoma (WDNC); poorly differentiated neuroendocrine carcinoma. The criteria of classification and the problems of multidirectional differentiation are discussed in detail.
Carcinoid Tumor↗
Integrins in developing, normal and malignant human kidney.
Explore the source record for details and available documents.
Carcinoma, Renal Cell↗
Differential distribution of tenascin and cellular fibronectins in acute and chronic renal allograft rejection.
BACKGROUND: Acute and chronic renal allograft rejection injuries involve, albeit variably, all compartments of the organ and are associated with significant structural changes. We hoped to gain new insights into these phenomena by determining distribution of certain extracellular matrix proteins known to be involved in architectural remodeling processes. EXPERIMENTAL DESIGN: Frozen tissue samples from biopsies of acute (n = 14) and chronic (n = 12) human renal allograft rejections were studied to compare distribution of tenascin, the extradomains A and B (EDA, EDB), and oncofetal (Onc) isoforms of cellular fibronectin (cFn). Normal kidneys (n = 4) served as controls. Cryosections were immunostained by the avidin-biotin-complex method with monoclonal antibodies specific for those molecules. RESULTS: In acute rejection, reactivity for tenascin and EDA-cFn was increased slightly to moderately in glomerular mesangia and in most vessels while it was intensely and diffusely increased in the interstitium. Rarely were focal EDB-cFn and Onc-cFn reactions seen in lesions deemed to reflect acute injury. In chronic rejection, tenascin and EDA-cFn were strongly increased in most glomerular mesangia and in vascular walls but unevenly in the interstitium. In rare glomerular synechiae and vessels, enhanced staining for tenascin and EDA-cFn as well as EDB-cFn and Onc-cFn was noted while in obsolete glomeruli only EDB-cFn and Onc-cFn were detected. The enhanced distribution of tenascin and EDA-cFn partly reflected that noted during nephrogenesis, whereas staining patterns for EDB-cFn and Onc-cFn differed from their fetal counterparts. CONCLUSIONS: Tenascin and EDA-cFn are strongly and preferentially expressed in the interstitial and vascular compartments of acute and chronic renal rejection injury suggesting that, in these sites, active repair and remodeling occur during both phases of the rejection process irrespective of the changes seen by conventional microscopy. Tenascin, EDA-cFn as well as EDB-cFn and Onc-cFn are all involved, albeit variably, in the glomerular and vascular alterations of chronic rejection. The finding of tenascin and of the three isoforms of cFn in glomerular synechiae with actively proliferating epithelium suggests that certain epithelial cells might partake in the synthesis of these molecules.
Acute Disease↗
Enhanced tenascin expression in cervical and vulvar koilocytotic lesions.
Tenascin is an extracellular matrix glycoprotein that is widely expressed during embryogenesis. In adults, it is restricted to select sites, including certain epithelial-stromal interfaces, but is notably enhanced in active inflammatory-reactive processes and in the stroma of many neoplasms. The authors immunostained with the monoclonal antibody (MAb) 100EB2 cryosections of vulvar and cervical biopsies displaying convincing koilocytosis with variable degrees of hyperplasia-dysplasia; in situ carcinomas were included. The presence of human papillomaviruses (HPV) 6, 11, 16, 18, 31, or 33 was confirmed by in situ hybridization in a subset of cases. Findings were compared with normal controls. The study was extended with the MAb 143DB7 that reacted with tenascin in paraffin sections. In normal samples, tenascin immunoreaction appeared as a delicate, continuous rim, in the immediate vicinity of the laminin staining; in parakeratotic areas, the rim was thicker. In foci of hyperplastic-dysplastic epithelium with or without koilocytosis, a distinct increase in tenascin staining was noted; enhanced tenascin often paralleled increasing hyperplasia and dysplasia. In most cervical and vulvar carcinomas in situ, the reactions were intense and extended deeply and raggedly into the underlying stroma. Tenascin was selectively enhanced in the endocervical stroma around inflammed or metaplastic glands. The authors conclude that tenascin is increased in HPV infection associated with epithelial proliferation. Enhancement was most consistently strong and extensive in in situ carcinomas, suggesting a correlation with active phases of epithelial growth and stromal remodeling.
Cell Adhesion↗