Lowp53 protein expression in salivary gland tumours compared with lung carcinomas

Summary Fifty-one salivary gland tumours (23 pleomorphic adenomas, 5 Warthin's tumours, 12 mucoepidermoid carcinomas, 7 adenoid cystic carcinomas, 3 undifferentiated carcinomas and 1 acinic cell tumour) and 27 lung carcinomas (18 squamous cell carcinomas, 6 adenocarcinomas and 3 small cell carcinomas) were analysed immunohistochemically for the expression ofp53 nuclear phosphoprotein. Eight out of 51 (16%) salivary gland tumours werep53 positive. Three of these were benign and 5 malignant. All 3 benign salivary gland tumours were pleomorphic adenomas and expressed only occasional nuclear positivity with less than 1% of tumour cells positive. Of the 5p53-positive malignant tumours, 3 were mucoepidermoid carcinomas and 2 undifferentiated carcinomas. The malignant salivary gland tumours expressed more than 1% of positive nuclei in every case. Seventeen lung carcinomas werep53 positive (63%). Thirteen of these were squamous cell carcinomas, 3 were adenocarcinomas and 1 small cell lung carcinoma. The results show that mutations of thep53 gene may be infrequent in salivary gland tumours when compared with lung carcinomas. The relatively indolent course of some histological types of malignant salivary gland tumours could be associated with the preservation of the non-mutatedp53 gene in most of these tumours. The presence ofp53 positivity in some pleomorphic adenomas might, on one hand, suggest thatp53 gene alterations are also present in these tumours; on the other hand, the accumulation of thep53 protein in these tumours might also be due to some unknown mechanism, not necessarily related top53 gene mutation.     

Distribution and estimation of nucleolar organizer regions in various human lung tumours.

A quantitative study of nucleolar organizer regions in human lung carcinomas was carried out on routinely processed paraffin embedded tissue sections. We examined 104 lung carcinomas including 38 squamous cell carcinomas, 36 adenocarcinomas, 18 large cell anaplastic carcinomas, 6 small cell carcinomas and 6 carcinoids. No significant differences were found in mean number of NORs between squamous, adenocarcinoma and undifferentiated carcinomas including large cell and small cell carcinomas. Carcinoids had comparatively lower means except for one typical carcinoid. Considering the high incidence of overlap between ranges of NOR counts in these groups of tumours and in agreement with the only other study of lung tumours (which comprised only carcinoids and small cell carcinomas), we conclude that this technique cannot be reliably used to discriminate between various histologic types of lung cancers. However, long term follow up of these patients is needed to establish the value of the AgNOR technique for prognostic guidance.     

Expression of the laminin γ2 chain in different histological types of lung carcinoma. A study by immunohistochemistry and in situ hybridization

Sixty-four malignant lung tumours and 12 of their regional lymph node metastases were analysed for expression of the laminin γ2 chain by immunohistochemistry and in situ hybridization. Expression of the laminin γ2 chain was strongest in squamous cell carcinomas, followed by adenocarcinomas and large cell carcinomas. Positive cells, except for large cell carcinomas, were located at the epithelial–stromal interface of tumour clusters. An important exception was small cell lung carcinoma, with only a low level of laminin γ2 chain expression. Apart from tumour type, this may reflect the relatively scanty fibrous stroma in these tumours and supports previous observations that small cell lung carcinoma cells, contrary to other types, lack surface expression of α₆β₄ integrin, the specific laminin-5 binding receptor. In frozen sections, immunohistochemistry showed linear basement membranes around tumour clusters in squamous cell carcinomas and adenocarcinomas. This shows that carcinoma cells are capable of heavy deposition of the laminin γ2 chain around tumour clusters and suggests that a laminin γ2 chain-containing substrate may be of significance for the spread and growth of malignant tumours. Copyright © 1999 John Wiley & Sons, Ltd.     

Distribution of the cytoskeletal protein β-tubulin in normal lung, cryptogenic fibrosing alveolitis and lung tumours

Tubulin is the major protein of microtubules. The immunocytochemical distribution of tubulin within the human respiratory tract has not been investigated in detail and no analysis of diseased lung or lung tumours has been undertaken. We therefore studied the distribution of beta-tubulin in formalin-fixed normal lung (n = 6), cryptogenic fibrosing alveolitis (n = 10) and lung tumours (n = 66), using a monoclonal antibody to beta-tubulin. In normal lung positive immunostaining was observed in all ciliated epithelium from the trachea down to bronchiolar level; blood vessel endothelium, vascular smooth muscle and nerve bundles were also strongly positive; pneumocytes, cartilage and airway smooth muscle gave weak staining. A similar distribution of beta-tubulin was seen in cryptogenic fibrosing alveolitis, but with strong tubulin immunostaining of fibroblasts in the interstitium and of the cytoplasm of ciliated respiratory epithelial cells. In lung tumours, six of 17 (35%) adenocarcinomas, one of two adenosquamous and one of 17 (5%) squamous cell carcinomas gave strong immunostaining. All six large cell carcinomas gave strong immunostaining for tubulin. In neuroendocrine tumours, two of seven (28%) carcinoids, two of seven (28%) atypical carcinoids and seven of 10 (70%) small cell carcinomas were strongly positive for tubulin. beta-Tubulin is widely distributed in the normal and diseased respiratory tract and is found in many lung tumours, particularly in large cell and small cell carcinomas which are highly aggressive in behaviour.     

Prevalence of human papillomaviruses in lung carcinomas: a study of 218 cases.

High-risk human papillomaviruses (HPV) are largely implicated in the carcinogenesis of cervical carcinomas. Their role in bronchopulmonary carcinomas is still unclear. In the present study, we have explored 218 fresh frozen lung tumours for the presence of HPV with the Roche line blot assay and for the expression of mRNAs encoding E6 oncoprotein in HPV positive tumours. Only four samples were positive for HPV detection, one poorly differentiated squamous cell carcinoma and three large cell carcinomas. E6 mRNA was undetectable in these four samples. Our data confirm the low prevalence of HPV in lung carcinomas in Western European countries and do not plead in favour of a carcinogenic role for HPV in these carcinomas.     

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

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

Laminin in testicular germ cell tumours. An immunohistochemical study

Thirty-five testicular germ cell tumours comprising 16 yolk sac tumours, 15 embryonal carcinomas and 13 seminomas were examined for the presence and distribution of laminin using an indirect immunoperoxidase technique. In addition, nine normal yolk sacs and 23 carcinomas of the lung were studied. All the yolk sac tumours were positively stained for laminin. Both extra- and intracellular staining were found. Hyaline, eosinophilic material present within the tumours was positively stained, although with varying intensity. In 12 out of 15 embryonal carcinomas, laminin was found as a membrane staining but cytoplasmic staining also occurred. In 10 out of 13 classical seminomas, a membrane staining of many tumour cells was found, while cytoplasmic staining occurred in only a few seminomas. In all but one of the yolk sacs, laminin was present in the membrane beneath both the mesoblastic outer cell layer and the visceral endoderm. Intracellular staining was seen in some of the cells in both cell layers. In nine out of 23 carcinomas of the lung, laminin occurred extra- as well as intracellularly. Thus, this study showed that in normal yolk sacs the presence of laminin was not found to be particularly associated with any of the cell layers. Likewise, demonstration of laminin within yolk sac tumours did not define different patterns or subtypes of the yolk sac tumour. In addition, demonstration of laminin was not found to be useful in differentiating either between yolk sac tumours and embryonal carcinomas or between seminomas and non-seminomatous germ cell tumours. The findings add, however, interesting knowledge to histogenesis and embryogenesis.     

Polysialylated N-CAM, chromogranin A and B, and secretogranin II in neuroendocrine tumours of the lung

 Highly α2–8-sialylated N-CAM (neural cell adhesion molecule) impairs N-CAM-mediated cell adhesion. We investigated polysiaN-CAM immunoreactivity in a range of neuroendocrine lung tumours: 15 typical carcinoids, 21 atypical carcinoids, 2 large cell neuroendocrine carcinomas and 12 small cell lung carcinomas were selected on a morphological basis and by their immunoreactivity for chromogranin A and B and secretogranin II. A progressive loss of chromogranin expression, particularly of chromogranin B, was paralleled by the up-regulation of polysiaN-CAM in histologically more aggressive tumours (P = 0.001). These data support the hypothesis that loss of cell–cell adhesion properties might be a relevant factor in the origin of the aggressivity of lung neuroendocrine tumours. Received: 17 October 1996 / Accepted: 7 January 1997     

Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays

AIMS: Using tissue microarrays, this study analysed the expression of the multidrug resistance protein, MRP2, by immunohistochemistry with two different MRP2 antibodies. This is the first study to address the expression of MRP2 in various common human neoplasms. METHODS AND RESULTS: Immunohistochemistry was performed on zinc formalin-fixed tissue to evaluate normal tissues and carcinomas using two antibodies against MRP2 (EAG5, a polyclonal antibody, and M2-lll-6, a monoclonal antibody). Immunostaining was localized in neoplastic cells mainly on the cell membrane with M2-lll-6 and cell membrane and cytoplasm with EAG5. In normal tissues MRP2 was expressed in liver, gastrointestinal tract, and kidney tubular epithelial cells with both antibodies. MRP2 was seen in nine of 22 renal cell carcinomas, eight of 13 gastric carcinomas, 25 of 49 breast carcinomas, 14 of 32 lung carcinomas, 39 of 50 colon carcinomas, and 16 of 17 ovarian carcinomas. There was < 10% variability between the two antibodies. MRP2 expression was highest in moderate to poorly differentiated tumours from colon, lung, gastric, and ovarian carcinomas and in grade 2 and 3 breast and renal carcinomas. CONCLUSION: The expression of MRP2 in many solid human tumours indicates that inherent drug resistance may play an important role as a biomarker for predictive chemotherapy treatment.     

Immunocytochemical localization of neuron specific enolase in small cell carcinomas and carcinoid tumours of the lung

Carcinoid tumours and small cell carcinomas of the lung share many characteristics with normal neuroendocrine cells. While carcinoid tumours contain many dense-cored neurosecretory granules and are frequently argyrophil, small cell carcinomas are poorly granulated and rarely argyrophil, which casts doubt on their neuroendocrine nature. Immunostaining of the enzyme neuron specific enolase (NSE) was recently used to demonstrate the neuroendocrine components of the lung including nerves and neuroendocrine cells. We therefore used NSE immunostaining to investigate neuroendocrine differentiation in 79 lung tumours, including 18 bronchial carcinoids and 31 small cell carcinomas, and compared these results with those obtained with silver stains. Thirteen of the 18 carcinoids were reactive to silver, all other types being negative. NSE-immunoreactivity occurred in 16 carcinoids and 18 small cell carcinomas. None of the squamous cell carcinomas, large cell anaplastic carcinomas and adenocarcinomas examined showed NSE-immunoreactivity. Radioimmunoassay of extractable NSE from 10 fresh lung tumours correlated well with the immunostaining results, demonstrating large amounts in two small cell carcinomas (334 and 517 ng/mg protein) and three carcinoids (152, 908, and 1143 ng/mg protein). Values were much lower for four squamous cell carcinomas (31-44 ng/mg protein) and one large cell anaplastic carcinoma (30 ng/mg protein) and were accounted for by the presence of NSE-positive nerves and neuroendocrine cells in the surrounding lung. NSE immunostaining is a useful marker of neuroendocrine differentiation in lung tumours and should prove particularly valuable in the diagnosis of small cell anaplastic tumours and their metastases.     

Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumours

The expression of cytokeratins (CK) 1, 4, 5/6, 8, 13, 18, 19 and 20 and involucrin in 42 cases of squamous cell carcinomas from various locations was examined. The tumours expressed CK5/6 in 55%, CK8 in 76%, CK13 in 43% and CK19 in 95% of cases. The CK5/6-positive primary tumours were from uterine cervix, head and neck, lung, skin, oesophagus is and urinary bladder, and the CK13-positive primary tumours were from uterine cervix, lung and vulva. Metastatic squamous cell carcinomas from head and neck more frequently expressed CK5/6 and 13, 7/7 (100%) and 6/7 (86%) compared with 3/5 (60%) and 0/5 (0%) in the primary squamous cell carcinomas. Few cases were CK1, CK4 and CK18 immunoreactive, CK20 immunoreactivity was not observed. Involucrin was expressed in 71% of tumours, and most of the involucrin-positive cells were located at the central parts of tumour cell clusters except for one case in which the peripheral cells around tumour cell clusters were positive. Thus, expression of the so-called simple epithelial markers CK8 and CK19 occurs in the majority of squamous cell carcinomas. The absence of CK20 immunoreactivity may be helpful in differential diagnosis.     

Intracellular keratins in normal and pathological bronchial mucosa

Summary The distribution of intracellular keratins was investigated in normal bronchial epithelium and in several morphologically distinct forms of respiratory tract carcinomas. This study was performed with two different experimentally produced antisera against normal human stratum corneum keratin and against keratin protein of MW 67000 dalton, using indirect immunofluorescence and immunoperoxidase methods on tissue sections and cell suspensions.In normal bronchial epithelium, the basal cells were strongly labelled by both antisera. The ciliated columnar cells appeared devoid of cytokeratins in tissue sections but were strongly labelled with both antisera in cell suspensions. The goblet cells remained negative in every case. In squamous metaplasia of the bronchus, all epithelial cells were unevenly stained with both antisera.Among tumours, only the squamous cell carcinomas were strongly labelled by both antisera. Primary lung adenocarcinoma appeared weakly positive, whereas metastatic lung carcinomas, undifferentiated lung carcinomas, oat cell tumours, carcinoid tumours were negative.The immunocytochemical determination of keratins appears to be of value in the study of normal and abnormal epithelial differentiation, in the diagnosis of poorly differentiated carcinomas and in their distinction from metastatic tumours of the lung.     

Oncoprotein immunoreactivity in human endocrine tumours.

Abnormally expressed oncogenes are implicated in neoplastic transformation. We have investigated a series of endocrine tumours using immunocytochemistry as a first screening tool to detect oncogene expression. Paraffin sections of 44 pulmonary small cell carcinomas, 15 pulmonary atypical carcinoids, 12 bronchial carcinoids, 28 medullary thyroid carcinomas, 27 phaeochromocytomas, and 17 insulinomas were immunostained with antibodies to c-erbB-2, c-myc, L-myc, and N-myc. Diffuse immunoreactivity was detectable for c-erbB-2 in 8 out of 44 (18 per cent) pulmonary small cell carcinomas, 3 out of 15 (20 per cent) pulmonary atypical carcinoids, and 6 out of 27 (22 per cent) phaeochromocytomas; for c-myc in 18 out of 44 (41 per cent) pulmonary small cell carcinomas and 5 out of 15 (33 per cent) pulmonary atypical carcinoids; for N-myc in 6 out of 28 (21 per cent) medullary thyroid carcinomas; and for L-myc in 4 out of 27 (15 per cent) phaeochromocytomas. There was considerable intratumoral and intertumoral heterogeneity and, in each tumour group, no relationship was found between tumour pattern, mitotic index, and oncoprotein immunoreactivity. These results suggest that oncogene products are present in a proportion of endocrine tumours, and that specific oncoproteins seem to be related to tumour type but not to other histopathological findings. Thus, oncoprotein detection may be a useful tool for identifying subsets of endocrine tumours that are not otherwise recognizable morphologically.     

An assessment of MAC 387 antibody as a diagnostically useful marker of L1 epithelial antigen expression by lung tumours.

A recent report describing the distribution of L1 epithelial antigen in lung tumours in relation to the histological type claimed that this antigen was a highly reliable marker of squamous cell carcinoma. Our study was designed to test this claim and to examine the potential of this antigen in the typing of lung tumours in biopsy specimens. A total of 143 lung tumours were typed according to the WHO classification and examined immunohistochemically for L1 epithelial antigen expression using commercially available monoclonal mouse anti-human myeloid/histiocyte antigen (MAC 387). Positivity was found in 46 of 55 squamous cell carcinomas (84 per cent), 12 of 27 adenocarcinomas (44 per cent), 15 of 16 adenosquamous carcinomas (93 per cent), 10 of 15 large cell carcinomas (67 per cent), none of 20 small cell carcinomas, and none of 10 carcinoid tumours. Of those tumours expressing L1 epithelial antigen, most showed a patchy pattern of positivity. From this study it is clear that detection of L1 epithelial antigen by MAC 387 antibody is not specific for squamous cell carcinomas, but it may have a limited use in the diagnosis of small cell carcinomas and carcinoid tumours as these are consistently negative.     

Epidermal growth factor receptors in lung tumours

Immunocytochemical analysis of epidermal growth factor (EGF) receptor expression was carried out on frozen sections of 109 primary lung tumours resected at the Brompton Hospital from February 1984 to May 1985. Tumours with detectable levels of this proto-oncogene protein were significantly more frequent among squamous cell carcinomas than among other types of lung tumour. No truncated EGF receptors were detected in the tumours using two monoclonal antibodies (Mabs) directed against different portions of the receptor (EGFR1 and F4). Mab F4 is the first antibody to the EGF receptor to show reactivity in paraffin sections. Southern blot analysis of a subset of the tumours detected amplification of the EGF receptor gene in squamous cell carcinomas but not in adenocarcinomas. The one carcinosarcoma examined had a re-arranged and amplified EGF receptor gene. Measurement of EGF receptor expression in lung tumours can be of diagnostic value and may prove to be useful in the development of antibody-directed therapy.     

Expression of epithelial and neural antigens in small cell and non small cell lung carcinoma

Seventy-one lung carcinomas from 66 different patients were stained with a panel of monoclonal antibodies. Twenty-nine were small cell lung carcinoma (SCLC), 15 adenocarcinomas, 17 squamous carcinomas and 10 large cell carcinomas. Three of the monoclonal antibodies recognize different cytokeratins, three recognize other epithelial antigens and one recognizes a neural antigen. Both formalin-fixed and cryopreserved tumours were studied using an indirect immunoperoxidase method. 23/29 SCLC reacted with all but one of the antibodies which recognize epithelial antigens. This staining was similar to that seen in non small cell lung carcinomas (NSCLC) and provides further evidence that SCLC are true epithelial tumours. All but one of the SCLC stained with the antibody recognizing a neural antigen. This antibody did not stain squamous or adenocarcinomas. However, four of the large cell carcinomas stained well with this antibody, suggesting that SCLC and some large cell carcinomas share a common pathway of differentiation. There were variations of staining seen both within and between tumours. This has obvious implications if immunotargetting with monoclonal antibodies is to be used diagnostically or therapeutically.     

An assessment of involucrin as a diagnostically useful immunohistochemical marker in lung tumours

A previous report has described involucrin as a specific immunohistochemical marker of squamous differentiation in lung carcinomas. The aim of our study was to examine the expression of this antigen in a wide variety of lung tumours, with particular attention to its potential value in the typing of biopsy specimens. We found that immunostaining for involucrin was common in squamous carcinomas but was also found in adenocarcinomas, adenosquamous carcinomas, large cell carcinomas and carcinosarcomas. Small cell carcinomas, carcinoid tumours and mesotheliomas were negative. Contrary to previous claims, this marker appears to have little diagnostic utility in the typing of lung tumours.     

Comparative analysis ofp53 protein immunoreactivity in prostatic,lung and breast carcinomas

Summary In this study we analysed the expression ofp53 protein in a total of 143 carcinomas immunohistochemically. These consisted of 34 prostatic adenocarcinomas, 59 lung and 50 breast carcinomas. In 28 cases, an average of 2–3 additional sections from different tumour areas were analysed. Forty-nine of the 143 carcinomas (34%) showed typical nuclear immunoreactivity by immunohistochemical staining with thep53 antibody CM-1. Two of the 34 prostatic carcinomas (6%) werep53 positive while 25 of the 59 lung carcinomas (43%) and 22 of the 50 breast carcinomas (44%) showed positivity forp53. By grade: 49% of grade III tumours, 36% of grade II and 5% of grade I tumours werep53 positive. There were significantly morep53-positive cases in grade II–III tumours than in grade I tumours (P= 0.001) when all tumours were taken into account. Further, there were significantly morep53-positive cases in grade III than in grade I–II tumours (P=0.001). In lung tumours there were significantly morep53-positive cases in grade II–III tumours than in grade I tumours (P=0.018). Similarly, there were significantly morep53-positive tumours in grade III breast tumours than in grade I–II tumours (P=0.003). The low incidence ofp53 positivity in prostate carcinomas suggests that mutations of thep53 gene are not as frequent in the neoplastic transformation of these tumours as in lung or breast carcinomas. The association ofp53 positivity with tumours of higher grade suggests thatp53 mutations lead to tumours of a more aggressive type. The analysis of tumours by multiple sections indicates thatp53 positivity is not evenly distributed in tumour tissue. Therefore, analysis of additional tumour areas may reveal positivity some cases, which is not evident if only one section is studied.     

Laminin alpha2 chain (merosin M chain) distribution and VEGF, FGF(2), and TGFbeta1 gene expression in angiogenesis of supraglottic, lung, and breast carcinomas

The prognostic significance of vessel quantification in human solid tumours is still debated, due to the presence of multiple factors modulating neoangiogenesis and the invasiveness of neoplastic cells. This study examined ten supraglottic squamous carcinomas, ten non-small cell lung carcinomas (three squamous, five bronchioloalveolar, two adenocarcinomas), and nine classic (NOS) invasive ductal breast carcinomas. The properties studied in these tumours were vascularity; the immunohistochemical distribution of adhesion molecules such as alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1, alpha6beta4, and ICAM-1 in endothelial cells; extracellular matrix proteins (ECMPs) and laminin alpha2 chain (merosin M chain) in basal membranes of vessels; and gene expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF2), and transforming growth factor beta1 (TGFbeta1), by in situ hybridization. Independently of tumour type and vascularity, laminin alpha2 chain expression was observed in the basal membranes of a limited proportion of vessels. In vitro experiments demonstrated laminin alpha2 chain expression mainly in early endothelial cell cultures, suggesting that laminin alpha2 chain expression in vivo can be considered a marker of early angiogenesis. Stromal and parenchymal vascularity was associated with laminin alpha2 chain expression in supraglottic carcinomas, whereas in the other tumours, laminin alpha2 chain-positive vessels were observed only in the stroma. In supraglottic carcinomas, VEGF-positive cells were mainly represented by neoplastic cells, whereas in the other tumours, the great majority of VEGF-positive cells were macrophages and fibroblasts. FGF2- and TGFbeta1-positive cells were macrophages and fibroblasts in all tumours. These observations suggest that in addition to the quantification and distribution of vessels, evaluation of their maturation may contribute to a better understanding of the role of angiogenesis in the growth and spread potential of solid tumours. In this regard, in supraglottic carcinomas, parenchymal angiogenesis seems to be regulated mainly by neoplastic cells, which may help to explain their high metastatic potential; in solid tumours of different histogenesis, different cells might be responsible for modulating tumour angiogenesis.     

Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases

Aims:  To study caveolin-1 (Cav-1) expression in metastatic lung carcinomas.
Methods and results:  Cav-1 expression was investigated in a series of 121 lung carcinomas and it was shown that 18/121 tumours (14.9%) were Cav-1+. None of the pure bronchioloalveolar carcinomas proved to be positive, vs. 42.8% of the large cell carcinomas (neuroendocrine subtype excluded). Adenocarcinomas (8.5%), large cell neuroendocrine carcinomas (20%) and squamous cell carcinomas (29.6%) displayed an intermediate percentage of positive cases, suggesting a gradient of Cav-1 expression according to tumour histotype-related aggressiveness. Moreover, the percentage of Cav-1+ tumours with distant metastases was almost double that of non-metastatic tumours (17.8% vs. 8.1%), irrespective of the histotype. In 34 tumours metastatic to the brain, primary and secondary lesions were compared and 53% of brain metastases were Cav-1+ vs. 20.6% of primaries, indicating a de novo acquisition of Cav-1 expression. This pattern was exclusive to the brain, as it was not acquired in adrenal metastases. In our series, the presence of epidermal growth factor receptor amplification, determined by fluorescence in situ hybridization, was not related to Cav-1 reactivity.
Conclusions:  Cav-1 immunoreactivity in lung carcinoma is histotype-dependent and acquired de novo in brain metastases, suggesting a site-specific phenotypic shift in secondary lesions.