Biomedical subjects

Y Soini

Publications and source records attributed to Y Soini.

At least 91 records · Page 5Linked to original sources

PubMed1997

Tenascin expression is associated with a chronic inflammatory process in abdominal aortic aneurysms.

PURPOSE: This study was performed to test whether tenascin, a large oligomeric glycoprotein of the extracellular matrix, is present in AAA disease and whether it could play a pathophysiologic role in the development of this disease. METHODS: Tenascin immunoreactivity was investigated from samples of the aneurysmal walls of 17 patients with AAAs, and the results were compared with the results of those of six patients with aortoiliac occlusive disease (AOD) and one normal control patient. To study the source of tenascin mRNA synthesis, some tissue samples were also examined with a tenascin RNA probe by in situ hybridization. RESULTS: The difference in immunoreactivity between the AODs and AAAs was especially prominent in the adventitial layer, where the specimens from AAAs displayed strong diffuse and reticular immunostaining. In AAAs the immunostaining was clearly associated with the degree of mononuclear inflammatory cell infiltrate and with the neovascularization of the adventitial layer. CONCLUSION: Tenascin expression is evident in AAA disease and is distinctly associated with mononuclear inflammatory cells. The adhesive properties of tenascin may offer a relevant explanation for the mechanism by which monocytes transmigrate into the aortic wall. The definitive role of tenascin in AAA process may be more complex, however, and will necessitate further investigation.

Adult↗

PubMed1997

The extent of apoptosis is inversely associated with bcl-2 expression in premalignant and malignant breast lesions.

AIMS: In this study we investigated the extent of apoptosis in benign, premalignant and malignant breast lesions and its association with the immunohistochemical expression of bcl-2 oncoprotein. METHODS AND RESULTS: In order to detect apoptotic cells and bodies in tissue sections, the 3'-end DNA labelling method was used. Immunohistochemical staining was performed by using the avidin-biotin-peroxidase complex technique. A monoclonal antibody against bcl-2 oncoprotein was used and the specificity of the antibody was confirmed by immunoblot analysis. According to the results the extent of apoptosis, as determined by the apoptotic index, was lowest in benign ductal hyperplasias and sclerosing adenoses (0.15% and 0.07%, respectively). It was moderately elevated in atypical hyperplasias and in-situ carcinomas (0.20% and 0.40%, respectively) and highest in invasive carcinomas (0.76%). In ductal invasive carcinomas, grade I lesions showed a lower apoptotic index (0.52%) than grade II (0.72%) and grade III (1.17%) carcinomas. The apoptotic index was not significantly lower in lobular (0.82%) than in ductal invasive carcinomas (0.85%). bcl-2 immunohistochemistry was inversely related to the apoptotic index. In all cases studied the inverse association was very strong (P = 0.0004) but it was also present when only carcinomas were analysed (P = 0.01). In benign and atypical hyperplasias, bcl-2 positivity was observed in all cases, but such cases were less frequent in in-situ lesions and in invasive carcinomas. CONCLUSIONS: The results show that there is an inverse relationship between the extent of apoptosis and bcl-2 expression in breast lesions suggesting that its expression affects the regulation of apoptosis in them.

Apoptosis↗

PubMed1997

Tenascin expression in lichen sclerosus.

In this study, the distribution of tenascin immunoreactivity in 44 cases of vulvar lichen sclerosus (LS) was investigated. To assess the epithelial basement membrane structure, immunostaining with an antibody to type IV collagen was performed. Ten selected cases were also analyzed by in situ hybridization with a tenascin RNA probe to study the cellular distribution of tenascin mRNA synthesis in LS. Strong tenascin immunoreactivity could be found in LS, especially in areas with subepithelial edema and marked inflammation. By in situ hybridization, signals for tenascin mRNA could be found in basal keratinocytes, dermal fibroblasts, and endothelial cells. Staining for type IV collagen often revealed attenuation and discontinuity in the basement membrane. The abnormal accumulation of tenascin in LS suggests that it may participate in the pathogenesis of this disease. As shown by in situ hybridization, the cell types responsible for tenascin synthesis are basal keratinocytes, dermal fibroblasts, and endothelial cells. Because tenascin, together with fibronectin, is able to upregulate the expression of 92 kDa collagenase and stromelysin in fibroblasts, the matrix destruction and basement membrane damage in LS may partly be a consequence of an abnormal accumulation and synthesis of tenascin. The upregulation of tenascin synthesis in dermal fibroblasts, endothelial cells, and keratinocytes in LS could be mediated by an abnormal expression of growth factors, most notably TGF-beta, which are able to stimulate tenascin synthesis in many non-neoplastic and neoplastic cell lines.

Collagen↗

PubMed1997

Association between p53 overexpression, cell proliferation, tumor necrosis and extent of apoptosis in operated pancreatic adenocarcinoma.

In this study we investigated the immunohistochemical expression of the p53 protein in 44 ductal pancreatic adenocarcinomas and its relation to cell proliferation, apoptosis and necrosis, three factors affecting tumor growth. The results were evaluated against survival and other clinical parameters of the patients. p53-positivity was found in 18/44 (41%) of the tumors. A positive p53 status was significantly associated with a high extent of necrosis (> or = 10% of tumor tissue)(p = 0.04, Fisher's exact test), with a high immunohistochemical expression of PCNA (p = 0.04, Fisher's exact test) and with a high mitotic count (p = 0.05, two-tailed t test). No statistically significant association was found between p53-positivity and high or low extent of apoptosis as evaluated by in situ labeling of the 3'-ends of the DNA fragments (p = 0.34, Fisher's exact test). Patient survival was not associated with the p53 expression of the tumors or separately with tumor cell proliferation, apoptosis or necrosis. The results suggest that an altered p53 function, as reflected by p53 overexpression, affects tumor growth by promoting cell proliferation and necrosis, but does not show a significant association with the extent of apoptosis in operated pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2.

Hepatic angiosarcoma (HA) is an uncommon neoplasm associated with known etiologic factors in 25% to 42% of cases. It is, however, one of the most common sarcomas found in the liver. The aim of this study was to find was to find mutations in the K-ras-2 oncogene in sporadic and Thorotrast (TT)-induced HA. Point mutations in K-ras-2 were sought in archival, formalin-fixed tissue blocks from 24 patients with angiosarcoma. Of these, 19 cases were sporadic and 5 were TT-induced. Mutational analysis was performed by topographic microdissection with PCR amplification followed by genotyping. Specific mutations were determined by two independent methods: (a) direct sequencing of the PCR product confirmed by rePCR and by using a different sequencing primer, and (b) PCR-based selective enrichment of mutant DNA by endonuclease digestion followed by heteroduplex DNA analysis using denaturing gradient gel electrophoresis. Eleven K-ras-2 point mutations were detected in 7 of 24 (29%) tumors, including 5 of 19 (26%) sporadic HA and 2 of 5 (40%) TT-induced HA. There were seven G:C > A:T and four G:C > T:A mutations. All seven mutated tumors contained a codon 12-aspartate amino acid substitution. In addition, a second codon 12-cysteine mutant cell population was present in one of two codon 12-aspartate mutated TT-induced HA and in three of five codon 12-aspartate sporadic tumors. Of these four tumors, three contained both aspartate and cysteine mutations and were composed of multiple nodules; the fourth was a single mass. Seventeen tumors had multiple nodules; whereas 5 had a K-ras-2 mutation, 12 were wild-type. The molecular pathology of both sporadic and TT-induced HA is characterized by a high rate of K-ras-2 mutations characteristic of oxidative damage (ie, G:C > A:T and G:C > T:A mutations) resulting in two mutated population sets: codon 12 GGT > GAT and GGT > TGT (glycine to aspartic acid and cysteine). This is, to date, the first study to characterize the K-ras-2 gene mutations within human sporadic and TT-induced HA by direct sequence analysis and denaturing gradient gel electrophoresis. These data further support the hypothesis linking adduct-forming vinyl chloride exposure to HA containing a much higher frequency of K-ras-2 mutations and a mutational spectrum characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride.

Adult↗

PubMed1996

Expression of the laminin gamma 2 chain in pancreatic adenocarcinoma.

Forty-two pancreatic adenocarcinomas were investigated immunohistochemically and by in situ hybridization for the expression of the laminin gamma 2 chain. In 41 cases, intracytoplasmic immunoreactivity for the gamma 2 chain was seen. Positive tumour cells were located especially at the epithelial-stromal interface of the tumour cell islands. In 22 cases, diffuse laminin gamma 2 chain immunoreactivity could also be seen in stroma and in seven cases, occasional positivity was detected in the neoplastic basement membranes. Signals for laminin gamma 2 chain mRNA in tumour cells displayed a distribution similar to that observed on immunohistochemistry. There were significantly more cases with less than 20 per cent of laminin gamma 2 chain-positive tumour cells in tumours extending to peripancreatic tissues and/or tumours with regional or distant metastases (p = 0.029). A corresponding statistical significance could also be noted in the mRNA level (P = 0.025). The results show that pancreatic adenocarcinomas display a high activity of laminin gamma 2 chain synthesis. Tumours with a strong laminin gamma 2 chain synthesis show a lower invasive and metastatic potential than tumours with a weak or moderate laminin gamma 2 chain expression.

Adenocarcinoma↗

PubMed1996

Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in malignant fibrous histiocytomas and dermatofibromas as studied by in situ hybridization and immunohistochemistry.

The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was studied in eight malignant fibrous histiocytomas (MFH) and in eight dermatofibromas (DF) using in situ hybridization methods (ISH). Immunohistochemical stainings were also performed using corresponding antibodies to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed similarly both TIMPs, except for osteoclast-like giant cells, which showed a distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were concordant with the results obtained by ISH. The findings suggest that the behavior of MFHs and DFs is not directly or solely dependent on the quantity of type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might represent a chaotic response of malignant cells to increased matrix degradation. Alternatively, it may reflect a deranged communication between type IV collagenases and TIMPs in malignant tissues.

Adult↗

PubMed1996

Extent of apoptosis in relation to p53 and bcl-2 expression in germ cell tumors.

This study investigates the extent of apoptosis in 53 testicular and ovarian germ cell tumors by using the in situ 3'-end DNA labeling technique on tumor sections. The tumors were also immunostained with antibodies to the p53 and bcl-2 proteins. The extent of apoptosis was highest in embryonal carcinoma (mean, 2.9%) followed by seminoma (mean, 1.1%), choriocarcinoma (mean, 0.7%) and immature teratoma (mean, 0.7%). In individual components of the mixed germ cell tumors the apoptotic index was in the same range as in the corresponding pure germ cell tumors. Mature teratomas rarely contained any apoptotic cells. Sixty-two percent of all the tumors expressed p53 protein. p53 expression was quantitatively strongest in embryonal carcinomas which also showed the highest level of apoptosis. Bcl-2 positivity could only be detected in some mesenchymal and epithelial components of the immature and mature teratomas; embryonal carcinomas, seminomas, or choriocarcinomas did not express bcl-2 at all. Our results show that the level of apoptosis in germ cell tumors associates with the histological type of the neoplastic component independent of whether it is singly present or a component of a mixed germ cell tumor. The results suggest that the quantity of p53 expression may contribute to the level of apoptosis in different tumor groups.

Apoptosis↗

PubMed1996

Hepatocellular carcinomas with a high proliferation index and a low degree of apoptosis and necrosis are associated with a shortened survival.

In this study we investigated tumour growth in relation to the immunohistochemical expression of p53 and bcl-2 and to patient survival data in 33 operated hepatocellular carcinomas (HCCs). In order to estimate the growth, a growth index, based on the degree of cell proliferation, apoptosis and necrosis, was calculated for each tumour. Cell proliferation was determined immunohistochemically by the number of proliferating cell nuclear antigen (PCNA)-positive cells in tumours, the extent of apoptosis was determined by counting the number of cells labelled by the in situ 3'-end labelling technique and tumour necrosis was estimated as the percentage of necrotic areas in haematoxylin--eosin-stained tissue sections. In our analysis we found that the survival of patients with HCCs showing a high growth index (i.e. tumours showing a high proliferation and simultaneously a low degree of apoptosis and necrosis) was significantly shorter than with other patients (P = 0.004, log-rank test). When analysed separately, cell proliferation, apoptosis or necrosis did not show any significant association with survival. p53 positivity was found in 8/33 (24%) of tumours. There were significantly more p53-positive cases in tumours with a high growth index (P = 0.01, Fisher's exact test) suggesting that dysfunction of the p53 gene may affect tumour growth. p53-positive cases did not, however, have a significantly shorter survival time than p53-negative cases (P = 0.3, log-rank test). bcl-2 positivity was found in only 1/33 (3%) of the HCCs. Thus bcl-2 overexpression does not seem to play an important role in hepatocellular carcinogenesis. In summary, our results suggest that in HCCs a compound score based on the evaluation of the degree of cell proliferation, apoptosis and necrosis is a biologically more relevant prognostic indicator than any of its composite parameters alone.

Antibodies, Monoclonal↗

PubMed1996

bcl-2 is preferentially expressed in tumours of muscle origin but is not related to p53 expression.

bcl-2 is a proto-oncogene which inhibits apoptosis. In contrast, p53 tumour suppressor gene is known to induce apoptosis. In this study we analysed immunohistochemically 63 mesenchymal tumours for the expression of bcl-2 and p53 proteins with a special emphasis on muscle-derived tumours. bcl-2 was expressed in all seven rhabdomyosarcomas and in five out of seven leiomyosarcomas. In benign muscle tumours, bcl-2 expression was found in all four epithelioid leiomyomas and in six out of 14 leiomyomas. In non-neoplastic muscle cells, occasional weak bcl-2 positivity was found in muscle cells of vascular walls and myometrium. In mesenchymal tumours of other lineages, bcl-2 positivity was only found in four out of 12 malignant fibrous histiocytomas and in one out of three liposarcomas. p53 positivity was found in 14 tumours, 13 of which were sarcomas. No association was found between p53 and bcl-2 positivity. Our results suggest that bcl-2 expression is activated significantly more often in muscle derived tumours than in mesenchymal tumours of other lineages. Our results also suggest that p53 status does not directly affect the expression of bcl-2 in sarcomas.

Genes, p53↗

PubMed1996

An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico.

The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-->AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.

Adult↗

PubMed1996

The association of vascular proliferation with HPV status and epithelial PCNA positivity in cervical intraepithelial lesions.

In this study we investigated the number of blood vessels and vascular proliferation in subepithelial areas of 80 cervical condylomas and cervical intraepithelial neoplasias (CIN). The number of blood vessels was determined by counting factor VIIIRAg-positive vascular channels in areas beneath the epithelial lesions. Vascular proliferation was evaluated by determining the number of proliferating cell nuclear antigen (PCNA)-positive endothelial cells in the subepithelial connective tissues. The results were compared with the expression of human papillomavirus (HPV) DNA subgroups (6/11 (low-risk) and 16/18/31/33/35 (high-risk) of the lesions, as determined by dot-blot and in situ hybridization, and with epithelial cell proliferation as determined by immunohistochemistry for PCNA. Also p53 immunohistochemistry of the lesions was performed. Even though CIN II-III lesions on average contained more factor VIIIRAg-positive blood vessels compared to condylomas and CIN I lesions, no significant association was found between their number and the degree of dysplasia. However, moderate or strong PCNA staining in vascular endothelial cells was seen significantly more often in CIN II-III lesions than in condylomas and CIN I lesions (p = 0.008): 34/80 (45%) cases contained detectable HPV DNA as determined by dot-blot or in situ hybridization. There was no correlation between the presence or absence of HPV DNA and the number of PCNA-positive endothelial cells. Nine cases showed p53-positive cell nuclei and in three cases there was more than 1% positive nuclei in the lesion. No association was found between the vascularity or the number of PCNA-positive endothelial cells and the p53 immunoreactivity. The increased proliferative activity of endothelial cells in CIN II-III lesions suggests that they are angiogenically more active than condylomas and CIN I lesions. This activity does not, however, depend on the HPV or p53 status. This is the first report in which endothelial cell PCNA positivity was used as a marker for vascular proliferation.

Antigens, Neoplasm↗

PubMed1996

Expression of P-glycoprotein in hepatocellular carcinoma: a potential marker of prognosis.

AIMS: (1) To investigate the immunohistochemical expression of the multidrug resistance gene (MDR1) product P-glycoprotein in histological samples from 31 hepatocellular carcinomas (HCCs); and (2) to correlate the results with cell proliferation, p53 expression, the disease-free interval, and cumulative patient survival. METHODS: C219 (a monoclonal antibody), CM-1 (a polyclonal rabbit anti-human antibody) and PC10 (a monoclonal mouse anti-human antibody) were used to detect expression of P-glycoprotein, p53 and proliferating cell nuclear antigen (PCNA), respectively, by means of the avidin-biotin peroxidase method. RESULTS: Membrane bound positivity for P-glycoprotein was observed in 20 (65%) of the 31 HCCs. Cytoplasmic globular positivity was also seen in some cases. There were no significant associations between expression of P-glycoprotein and cell proliferation (determined by PCNA immunoexpression and the mitotic count), or p53 expression. Patients with P-glycoprotein positive tumours had a shorter disease-free interval than those with P-glycoprotein negative tumours, and also had a shorter survival time. There was no difference in survival between P-glycoprotein positive patients who had or had not received chemotherapy, suggesting that chemotherapy (mainly mitomycin-C) did not affect survival in these patients. CONCLUSIONS: Expression of P-glycoprotein in HCCs is associated with a shorter disease-free interval and shorter survival time. As expression of P-glycoprotein was not associated with cell proliferation or expression of p53, its effect on disease progression and survival seems to be independent of these factors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Tenascin in human papillomavirus associated lesions of the uterine cervix.

The immunohistochemical expression of tenascin was studied in 80 morphologically diagnosed condylomas and cervical intraepithelial neoplasia (CIN) lesions. The results were compared with the human papillomavirus (HPV) DNA subtype, which was determined by HPV dot blot and in situ hybridisation. Tenascin mRNA synthesis was also determined in 10 selected cases by in situ hybridisation. No statistically significant association was found between tenascin expression and the degree of dysplasia or the HPV subtype. There was, however, a strong correlation between the extent of tenascin immunoreactivity and the degree of inflammation. Synthesis of tenascin mRNA was detected in basal keratinocytes and in fibroblasts by in situ hybridisation. The lack of association between the grade of CIN and tenascin expression precludes its use as a marker of premalignancy in CIN.

Base Sequence↗

PubMed1996

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.

Adenocarcinoma↗

PubMed1996

Tenascin immunoreactivity as a prognostic marker in usual interstitial pneumonia.

In this investigation, tenascin (Tn) expression was studied in 51 cases of different types of fibrotic lung disorders originating for years 1981 to 1995. Our aim was to test if accumulation of Tn at the site of lung injury in usual interstitial pneumonia (UIP) could correlate with the prognosis. Lung biopsies taken from 28 patients with UIP, six with desquamative interstitial pneumonia (DIP), six with sarcoidosis, five with extrinsic allergic bronchioloalveolitis, five with bronchiolitis obliterans organizing pneumonia (BOOP), and one with nonspecific interstitial pneumonia were studied for the expression of Tn by using an immunohistochemical technique. In addition to Tn immunohistochemistry, selected cases were also studied by immunoelectron microscopy and Western blotting. For prognostic studies in UIP the clinical follow-up information was obtained from the patient records. The expression of Tn was increased in each type of fibrosis, especially in UIP. In immunoelectron microscopy the most prominent labeling in UIP was found in association with collagen fibers and within the type 2 pneumocytes. Every studied case of UIP showed reactivity for a polypeptide of M(r) approximately equal to 200,000 by Western blotting. In patients with UIP, increased Tn expression, especially under metaplastic bronchiolar-type epithelium, was associated with a shortened survival time. Immunoelectron microscopic findings support the idea that Tn in UIP is synthesized by the regenerating epithelial rather than interstitial cells in response to pulmonary interstitial inflammation.

Adult↗

PubMed1995

p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis.

Accumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild-type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM-1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty-six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow-up of 12-176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1995

Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma.

This study was undertaken to determine the extent of apoptosis in lung carcinoma and to evaluate it as a prognostic marker. A series of 75 lung carcinomas (47 squamous cell carcinomas, 24 adenocarcinomas, 3 small cell carcinomas, and 1 large cell carcinoma) was analyzed for the extent of apoptosis by using the 3' end-labeling method of DNA in tissue sections. Apoptosis was correlated with the rate of cell proliferation, the immunohistochemically detectable p53 and bcl-2, the extent of tumor necrosis, and the survival data. The end-labeling method allowed a precise evaluation of the extent of apoptosis. In tumor tissue, the number of apoptotic bodies was roughly 2-fold greater than the number of apoptotic cells, whereas in nonneoplastic control tissues, the ratio was 1:1. The apoptotic indexes (percentages of apoptotic cells and bodies among tumor cells) were slightly higher in adenocarcinoma than in squamous cell carcinoma. There was no association between the extent of apoptosis and the expression of proliferating cell nuclear antigen or p53. On the other hand, tumor necrosis correlated significantly with proliferating cell nuclear antigen and p53 positivity (P = 0.00025 and 0.00087, respectively). Surprisingly, the extent of apoptosis was also found to be independent of the expression of bcl-2. Patients with apoptotic indexes greater than 1.5% had significantly shorter survival time than patients with apoptotic indexes equal to 1.50% or less (P < 0.01 by log rank). Aberrant p53 positivity also predicted a poor prognosis (P < 0.002 by log rank). By multivariate analysis, enhanced apoptosis showed a 1.9-fold risk (P = 0.04), and p53 positivity showed a 2.3-fold risk (P = 0.005) for a shortened survival. We conclude that both enhanced apoptosis and p53 positivity are independent prognostic markers in non-small cell lung carcinoma, predicting shortened survival time of the patients.

Aged↗