共查询到20条相似文献,搜索用时 15 毫秒
1.
G. Auer K. Heselmeyer A. Zetterberg R. Steinbeck E. Munck-Wikland 《Virchows Archiv : an international journal of pathology》1994,424(4):343-347
This paper describes the investigation of nuclear DNA content and p53 immunoreactivity in normal mucosa (n=25), mildly (n=15), moderately (n=28) and severely atypical (n=22) colorectal adenomas and in colorectal adenocarcinomas (n=116). Twenty-seven per cent of the mildly atypical, 43% of the moderately, 77% of the severely atypical adenomas and 91% of the colorectal carcinomas were distinctly aneuploid. In the aneuploid lesions p53 immunoreactivity was not observed in mildly atypical adenomas, whereas 17% of the moderately atypical, 24% of the severely atypical adenomas and 66% of the adenocarcinomas were p53 positive. None of the diploid lesions were p53 immunoreactive. These data are interpreted to indicate that genomic instability as reflected by crude aneuploidy occurs early during genesis of colorectal carcinoma and represents a high risk factor for p53-gene mutation. 相似文献
2.
3.
Apoptosis in human colorectal tumours: ultrastructure and quantitative studies on tissue localization and association with bak expression 总被引:2,自引:0,他引:2
Gerda Partik Patrizia Kahl-Rainer Roland Sedivy Adolf Ellinger Wilfried Bursch B. Marian 《Virchows Archiv : an international journal of pathology》1998,432(5):415-426
Apoptotic cell death in human tumours has been demonstrated by electron and light microscopy. In adenomas, fragmented and
apoptotic nuclei and signs of phagocytosis have been observed close to the basement membrane. In carcinomas the characteristic
structures were apoptotic bodies with small fragments of chromatin. DNA fragmentation was shown by in situ end-labelling.
Quantitative assessment of apoptosis and proliferation revealed a high apoptotic index (AI) in all types of adenoma (tubular:
1.77±0.35%, tubulovillous: 2.38± 0.41%; villous: 3.3±0.39%) as well as loss of compartmentalization of proliferating and dying
cells. In carcinomas a shift towards proliferation was evident, as shown by lower AIs than in adenomas (0.9±0.68% and 1.1±0.12%
for moderately and poorly differentiated tumours), higher Ki67 indices (38.32±2.23% and 57± 3.89%, respectively) and higher
mitosis (0.9±0.56% and 1.21±0.17%, respectively). However, apoptosis was observed in all tumours and is available as a target
for therapeutic intervention. Expression of the apoptosis related proteins bcl-2 and bak also reflected loss of compartmentalization.
While bcl-2 did not show a consistent relationship to AI in tumour specimens, bak was positively correlated with apoptosis
in 4 of 8 adenomas and 4 of 7 carcinomas, suggesting a role for this protein in the induction of apoptosis in a subset of
tumours.
Received: 22 July 1997 / Accepted: 27 October 1997 相似文献
4.
M. Ikeda Kohei Shomori Kouji Endo Takafumi Makino Takahiko Matsuura Hisao Ito 《Virchows Archiv : an international journal of pathology》1998,432(1):43-47
We examined the relationship between apoptosis and the progression of human gastric carcinoma. Studies were conducted on a total of 88 surgically removed stomachs, comprising 26 minute (less than 5 mm in diameter), 29 early (limited to the mucosal and submucosal layer) and 33 advanced carcinomas. Apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Serial sections were immunostained for p53 and Ki-67. The mean apoptotic indices (AI: percentage of TUNEL signal positive cells) of minute, early, and advanced carcinomas were 4.1±0.6, 3.8±1.2, and 4.0±1.2 in 46 well differentiated carcinomas, and 2.1±0.5, 2.7±0.9, and 2.2±1.1 in 42 poorly differentiated carcinomas, respectively. Similarly, the mean Ki-67 labelling indices (KI) were 39.2±7.8, 47.2±12.8, 52.6±13.1 in the former, and 35.0±9.3, 36.9±10.3, and 40.0±9.2 in the latter, respectively. Both mean AI and mean KI were significantly higher in well differentiated than in poorly differentiated carcinomas (P<0.05). However, the value of mean AI did not differ among minute, early, and advanced carcinomas in either histological type, while KI increased gradually with tumour progression. The frequency of nuclear p53 expression did not differ among the three categories, implying that the gene mutation is an early event in gastric carcinogenesis. There was no statistical significance between nuclear p53 expression and mean AI. These results suggest that the progression of gastric cancer is defined by a gradual increase of proliferative activity and constant occurrence of apoptosis and that naturally occurring apoptosis is induced predominantly via a p53-gene-independent pathway. 相似文献
5.
Imbalance between proliferation and apoptosis in the development of colorectal carcinoma 总被引:8,自引:0,他引:8
Xingpei Hao Mingqing Du Anne E. Bishop I. C. Talbot 《Virchows Archiv : an international journal of pathology》1998,433(6):523-527
To evaluate the relationship between cell proliferation and apoptosis in sporadic colorectal carcinogenesis, immunohistochemistry
for proliferation-associated antigen Ki-67 and in situ end labelling for identifying apoptotic bodies were performed on paraffin
sections from 59 adenomas and 22 carcinomas. These results were correlated with the expression of the proliferation and apoptosis
modulators Bcl-2 and p53. Carcinomas showed increased proliferation and apoptosis compared with adenomas (P<0.0001, P<0.001, respectively). There were positive linear correlations between proliferation and apoptosis in adenomas and carcinomas
(P<0.02, P<0.05, respectively). The proliferative rate increased significantly from mild to moderate, and from moderate to severe dysplasia
(P<0.002, P<0.001, respectively). Apoptotic rate also increased in this sequence, but the increases did not reach statistical significance
(both P>0.05). Expression of Bcl-2 was associated with lower apoptotic rate in adenomas (P<0.025) but not in carcinomas (P>0.25), whereas p53 expression was correlated with higher proliferative rate in both adenomas and carcinomas (P<0.01, P<0.05, respectively). An inverse relationship between Bcl-2 and p53 expression was seen in both adenomas and carcinomas (P<0.05, P<0.005, respectively). These data suggest that the normal balance between proliferation and apoptosis is disturbed in colorectal
carcinogenesis, both being increased, but proliferation occurs in excess. Bcl-2 and p53 may each play a role in modulating
cell apoptosis or proliferation during the development of colorectal carcinoma.
Received: 23 March 1998 / Accepted: 7 July 1998 相似文献
6.
M. Ishida Y. Gomyo S. Tatebe S. Ohfuji H. Ito 《Virchows Archiv : an international journal of pathology》1996,428(4-5):229-235
We examined the existence and distribution of apoptotic cells in human gastric mucosa, chronic gastritis, adenomatous dysplasias and carcinomas in 15 surgically removed stomachs in which dysplasia and carcinoma were found simultaneously. Serial sections were cut for immunohistochemistry for p53 oncoprotein and Ki-67 antigen, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL). TUNEL signal-positive apoptotic cells were rare in normal mucosa, while a few apoptotic cells were noted in gastritic mucosa and intestinal metaplasia, intermingled with Ki-67 antigen-positive cells forming a generative cell zone. This suggests the cell-cycle-dependent apoptosis of gastric mucosa. The frequency of apoptotic cells per crypt was higher in incomplete than in complete metaplasia, implying greater underlying DNA damage in the former. TUNEL indices (TI; percentage of TUNEL-positive cells in tumour cells) were slightly higher in adenomatous dysplasias (4.9±2.1) than in carcinoma (3.9±1.1), but there was no no statistical difference. Ki-67 indices (KI; percentage of Ki-67 antigen-positive cells in tumour cells) were significantly (P<0.05) higher in carcinomas than in dysplasias. Thus, gastric adenomatous dysplasias were characterized by relatively higher TI and lower KI, which might reflect a more static growth potential. The expression of p53 oncoprotein in cancer cells is thought to be an apoptosis-suppressing event, although its precise role remains to be elucidated. Overall, these results indicate that apoptosis plays a crucial part in the morphogenesis of gastritic mucosa including intestinal metaplasia, and that the process is correlated both with tumourigenesis and with proliferative activity. 相似文献
7.
Brustmann H 《Pathology, research and practice》2002,198(2):85-90
This study evaluated the relation of apoptosis with mitotic activity, Ki-67 indices, and nuclear and architectural grades in serous ovarian carcinoma. Apoptotic body (ABI) and mitotic indices (MI) were obtained by examining hematoxylin and eosin-stained sections from 35 serous ovarian carcinomas for apoptotic bodies and mitotic figures. ABI and MI were reported as the number of apoptotic bodies, and mitotic figures and immunostaining for Ki-67, respectively, as positive cells in 1000 cells. Nuclear grade was determined as grade 1 [n = 11], grade 2 [n = 13], and grade 3 [n = 11] according to recently defined criteria. There was a significant correlation between Ki-67 indices and ABI (p < 0.0001), Ki-67 and MI (p < 0.0001), as well as between MI and ABI (p < 0.0001). ABI increased with nuclear grade (p < 0.0001) and the type of the histological differentiation pattern (from glandular to papillary and solid architectural patterns) (p < 0.0001). Apoptosis, quantitated by ABI, is positively correlated with proliferation, thereby constituting a factor in the regulation of tumor growth of serous ovarian carcinomas. The positive correlation between ABI and increasing nuclear grade, mitotic activity, and architectural growth pattern may indicate that apoptotic bodies are another variable for grading serous ovarian carcinomas. 相似文献
8.
Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis 总被引:4,自引:0,他引:4
Nomura M Watari J Yokota K Saitoh Y Obara T Kohgo Y 《Virchows Archiv : an international journal of pathology》2000,437(1):17-24
Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether
cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI),
apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised
of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas
with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic
cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry
for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas.
PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat
elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and
2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with
LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and
in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar
among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis
not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.
Received: 1 July 1999 / Accepted: 17 January 2000 相似文献
9.
MAKOTO IKENAGA YASUO TAKANO YOSHIMASA OHTANI HIDETO TSUKAMOTO YOSHIKI HIKI AKIRA KAKITA LSAO OKAYASU 《Pathology international》1998,48(6):453-459
In order to clarlfy the cell kinetics of colorectal villous tumors (VT), 21 villous adenomatous areas and 12 carcinomatous areas within villous adenomas were investigated for proliferative activity and apoptosis and compared with a series of 41 tubular tumors (TT), demonstrating elements of intramucosal carcinomas as well as tubular adenomas (so-called carcinoma in tubular adenoma). Proliferation was estimated in terms of KI-67 labeling indices and mitotic indices, and apoptosis was assessed by DNA nick-end labeling to give apoptotic Indices. Apoptotic indices of villous adenomatous and carcinomatous regions were significantly lower than the values for their tubular counterparts. Kl-67 labeling indices were also significantly lower for adenoma components. Apoptotic indices, Ki-67 labeling indices and mitotic Indices increased with atypia raised in tubular adenoma components. Correlations of mitotic indices with apoptotic indices, Ki-67 labeling Indices with apoptotic indices and mitotic Indices with Ki-67 labeling indices were found for each villous tumor group and tubular tumor group, and the apoptosis and proliferation ratios for villous tumors were relatively low, suggesting a tendency for greater growth due to less cell deletion. Although this is only one of the biological features of villous tumor groups, it might play a major role in generation of malignancy. 相似文献
10.
Julia?Alcaide Rafael?Funez Antonio?Rueda Elisabeth?Perez-Ruiz Teresa?Pereda Isabel?Rodrigo Rafael?Cove?as Miguel?Mu?oz Maximino?Redondo
Background
Alterations to apoptosis are a common occurrence in human tumours. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of colorectal carcinomas (CRCs).Methods
A TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26 adenomas and 20 samples of normal epithelia.Results
The number of apoptotic cells was higher in CRCs (1.09?±?0.13) than in adenomas (0.38?±?0.23, p?=?0.059) and normal epithelium (0.06?±?0.04, p?=?0.001). In addition, the apoptotic index (AI) was greater in metastatic disease (stage IV) than in other stages (p?=?0.017). No relationship was found between apoptotic rates and age, gender or tumour grade. However, patients with tumours that showed higher AI values had a significantly lower disease-free survival (DFS) and overall survival (OS) than those with tumours that had lower AIs (p?=?0.020 and p?=?0.027). In a multivariate Cox proportional hazards model, AI remained a significant independent predictor of survival.Conclusions
We conclude that disregulated apoptosis is an important event during CRC development and progression. Higher AIs are associated with more aggressive tumours and a poorer prognosis for patients with CRC.11.
Friederich P van Heumen BW Nagtegaal ID Berkhout M van Krieken JH Peters WH Nagengast FM 《Virchows Archiv : an international journal of pathology》2007,451(3):659-667
To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy
is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may
develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients
with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were
immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices,
respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic
rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly
higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation
in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the
pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance.
The experiments performed for this study comply with the current laws of The Netherlands. 相似文献
12.
Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas 总被引:19,自引:0,他引:19
Osaki M Sakatani T Okamoto E Goto E Adachi H Ito H 《Virchows Archiv : an international journal of pathology》2000,437(1):31-36
Thymidine phosphorylase (dThdPase) / platelet- derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels
in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral
microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD
and p53 expression in human gastric carcinomas. dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in
20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from
the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category
II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8±19.4 in category I and 61.4±17.3 in
category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8±21.0 in category I and 76.0±27.1 in category
II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95±1.30 in category I, and 3.76±1.49 in category
II carcinomas for early gastric carcinoma, and 1.51±0.98 in category I and 2.14±0.66 in category II carcinomas for advanced
gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase- negative tumors (category II) than in the positive tu-mors (category I), regardless of tumor stage
or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral
microvessels and a decrease in apoptosis in human gastric carcinomas.
Received: 8 November 1999 / Accepted: 20 January 2000 相似文献
13.
目的:通过观察胃癌及其癌前病变中细胞凋亡及其调控基因p53、bcl-2、c-myc的表达,探讨其在胃癌恶性转化进程中的作用。方法:利用DNA末端标记技术(TdT-mediateddUTP-biotinnickendlabeling,TUNEL法)和免疫组织化学(streptavidin/peroxidase,S-P法),原位观察了46例胃癌、20例癌前病变、24例正常粘膜中的凋亡细胞和p53、bcl-2、c-myc的表达。结果:癌前病变和胃癌中凋亡指数显著高于正常粘膜(P<0.01),癌前病变组高于胃癌组(P<0.01)。p53、bcl-2、c-myc蛋白在胃癌中阳性率分别为60.9%、67.4%、73.2%,均高于正常粘膜组(P<0.01);在癌前病变中3种蛋白阳性表达率分别为40%、95%、58.8%(P<0.01)。胃癌中p53、bcl-2蛋白阳性细胞凋亡指数分别低于阴性组(P<0.05),c-myc蛋白阳性组细胞凋亡指数高于阴性组(P<0.01)。结论:细胞凋亡调控异常在胃癌发生中可能起重要作用。p53、bcl-2蛋白分别抑制细胞凋亡,c-myc蛋白在胃癌中促进细胞凋亡。 相似文献
14.
Andrew D Beggs Angela Jones Mona El‐Bahwary Muti Abulafi Shirley V Hodgson Ian PM Tomlinson 《The Journal of pathology》2013,229(5):697-704
Changes in DNA methylation, whether hypo‐ or hypermethylation, have been shown to be associated with the progression of colorectal cancer. Methylation changes substantially in the progression from normal mucosa to adenoma and to carcinoma. This phenomenon has not been studied extensively and studies have been restricted to individual CpG islands, rather than taking a whole‐genome approach. We aimed to study genome‐wide methylation changes in colorectal cancer. We obtained 10 fresh‐frozen normal tissue–cancer sample pairs, and five fresh‐frozen adenoma samples. These were run on the lllumina HumanMethylation27 whole‐genome methylation analysis system. Differential methylation between normal tissue, adenoma and carcinoma was analysed using Bayesian regression modelling, gene set enrichment analysis (GSEA) and hierarchical clustering (HC). The highest‐rated individual gene for differential methylation in carcinomas versus normal tissue and adenomas versus normal tissue was GRASP (padjusted = 1.59 × 10–5, BF = 12.62, padjusted = 1.68 × 10–6, BF = 14.53). The highest‐rated gene when comparing carcinomas versus adenomas was ATM (padjusted = 2.0 × 10–4, BF = 10.17). Hierarchical clustering demonstrated poor clustering by the CIMP criteria for methylation. GSEA demonstrated methylation changes in the Netrin–DCC and SLIT–ROBO pathways. Widespread changes in DNA methylation are seen in the transition from adenoma to carcinoma. The finding that GRASP, which encodes the general receptor for phosphoinositide 1‐associated scaffold protein, was differentially methylated in colorectal cancer is interesting. This may be a potential biomarker for colorectal cancer. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
15.
Apoptosis occurs independently of bcl-2 and p53 over-expression in non-small cell lung carcinoma 总被引:6,自引:0,他引:6
Certain oncogenes and tumour suppressor genes are known to modulate apoptosis. To investigate whether over-expressed bcl-2 and abnormally stabilized p53 are associated with reduced apoptosis in paraffin sections of non-small cell lung carcinoma, apoptotic, mitotic, and Ki-67 labelling indices were determined and correlated with bcl-2 and p53 immunoreactivity in 54 squamous cell carcinomas and 22 adenocarcinomas. Nineteen squamous cell carcinomas (35.2%) showed over-expression of bcl-2, but all 22 adenocarcinomas were bcl-2 negative. Thirty-seven squamous cell carcinomas (68.5%) and 13 adenocarcinomas (59.1%) showed p53 over-expression. Apoptotic tumour cells were identified among p53 positive and bcl-2 positive tumour cells. There was a significant linear correlation between apoptotic indices and mitotic indices. bcl-2 over-expression and p53 over-expression were not associated with attenuated apoptosis, or altered mitotic or Ki-67 labelling indices in either tumour type. Neither bcl-2 nor p53 was of prognostic significance. These results suggest that apoptosis in non-small cell lung carcinoma occurs independently, and is not modulated primarily by, bcl-2 or p53. It is likely that the effects on apoptosis of bcl-2 and p53 are countered by those of other oncogene products and/or additional factors that regulate apoptosis in vivo 相似文献
16.
McPartland JL Guzail MA Kendall CH Pringle JH 《International journal of experimental pathology》2005,86(1):19-24
Apoptosis is implicated as a major pathogenic mechanism in chronic hepatitis B and C. Previous studies of the relationship between apoptotic rates and histological necroinflammatory activity have produced conflicting results. Hepatocyte apoptosis was assessed in liver tissue from 32 cases of chronic viral hepatitis, seven cases of hepatocellular carcinoma (HCC) and six cases of steatohepatitis as non-viral disease controls and eight cases of control liver. Apoptotic rates were measured using H&E morphological assessment and immunohistochemical staining with antibodies to activated caspase-3 and M30. Histological necroinflammatory activity of viral hepatitis cases was scored using the Knodell scoring system, and the cases were divided according to their score into group 1 (mean 2.43 +/- 0.48) and group 2 (mean 7.80 +/- 0.49). Apoptotic indices were significantly higher in group 2 than group 1 using H&E (11.53 +/- 2.70 vs. 0 +/- 0, P=0.015) and activated caspase-3 (22.01 +/- 5.27 vs. 1.79 +/- 1.79, P=0.03) methods but were not significantly higher with M30 (3.80 +/- 1.74 vs. 0 +/- 0, P=0.207). Apoptotic scores using an antibody to activated caspase-3 are significantly higher in cases of chronic viral hepatitis with greater histological necroinflammatory scores, supporting a central role for apoptosis in disease pathogenesis. This method offers an alternative to routine histological assessment for measuring disease activity. 相似文献
17.
Souza LR Fonseca-Silva T Pereira CS Santos EP Lima LC Carvalho HA Gomez RS Guimarães AL De Paula AM 《Histopathology》2011,58(3):352-360
Souza L R, Fonseca‐Silva T, Pereira C S, Santos E P, Lima L C, Carvalho H A, Gomez R S, Guimarães A L S & De Paula A M B(2011) Histopathology 58 , 352–360 Immunohistochemical analysis of p53, APE1, hMSH2 and ERCC1 proteins in actinic cheilitis and lip squamous cell carcinoma Aims: This study has compared the tissue expression of the p53 tumour suppressor protein and DNA repair proteins APE1, hMSH2 and ERCC1 in normal, dysplastic and malignant lip epithelium. Methods and results: Morphological analysis and immunohistochemistry were performed on archived specimens of normal lip mucosa (n = 15), actinic cheilitis (AC) (n = 30), and lip squamous cell carcinoma (LSCC) (n = 27). AC samples were classified morphologically according to the severity of epithelial dysplasia and risk of malignant transformation. LSCC samples were morphologically staged according to WHO and invasive front grading (IFG) criteria. Differences between groups and morphological stages were determined by bivariate statistical analysis. Progressive increases in the percentage of epithelial cells expressing p53 and APE1 were associated with increases in morphological malignancy from normal lip mucosa to LSCC. There was also a significant reduction in epithelial cells expressing hMSH2 and ERCC1 proteins in the AC and LSCC groups. A higher percentage of malignant cells expressing APE1 was found in samples with an aggressive morphological IFG grade. Conclusions: Our data showed that epithelial cells from premalignant to malignant lip disease exhibited changes in the expression of p53, APE1, hMSH2 and ERCC1 proteins; these molecular change might contribute to lip carcinogenesis. 相似文献
18.
19.
Anna A. M. Van Der Wurff Stefan J. T. Vermeulen Edith P. M. Van Der Linden Marc M. Mareel Fred T. Bosman Jan-Willem Arends 《The Journal of pathology》1997,182(3):325-330
Previous in vitro and in vivo model studies have shown that when E-cadherin expression in carcinoma cells is reduced, invasive behaviour ensues. The situation in human cancer in vivo, however, appears to be more complex, as immunohistochemically determined E-cadherin expression in various carcinomas, including colorectal cancer, does not always correlate with invasive growth. Loss of cell adhesion during invasion in spite of E-cadherin expression might be associated with a defective cadherin–catenin complex. The expression of α- and β-catenin in comparison with E-cadherin was therefore examined in colorectal adenomas and carcinomas and in lymph node and liver metastases. In normal colonic mucosa, α- and β-catenin immunoreactivity occurred along the lateral plasma membranes of the epithelial cells, in a pattern identical to E-cadherin staining. A similar pattern was found in colorectal adenomas and in most malignancies. In general, in neoplastic epithelia, the majority of the cancer cells displayed a normal (matching) pattern of E-cadherin and catenin expression. It is concluded that the patterns of expression of E-cadherin and α- and β-catenin are very similar in colorectal neoplasms. This observation indicates that invasion in colorectal cancer is not paralleled by consistent loss of expression of the components of the cadherin–catenin complex. © 1997 John Wiley & Sons, Ltd. 相似文献
20.
Friedrich Prall Christiane Ostwald Horst Nizze Malte Barten 《Applied immunohistochemistry & molecular morphology》2004,12(2):111-121
With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 (<10%) and p27 (< or =50%) and reduced membranous expression of Ecadherin were significantly associated with a poorer clinical course by univariate analysis. beta-catenin immunostaining had no prognostic impact. Mitotic and apoptotic indices as well as Ki-67 labeling below the median were indicators of poor prognosis. Complete absence of p53 nuclear staining was a significant adverse prognostic factor. By Cox regression, p53 = 0%, p53 = 0%, in combination with p27 < or = 50%, the mitotic index and the combined mitotic and apoptotic index added prognostic information to UICC stage. The authors found that growth pattern, lymphohistiocytic response, lymphatic permeation, and venous spread, too, each was a strong prognosticator in addition to UICC stage. The results support that tissue microarrays are a useful tool for screening immunohistochemical markers for prognostic use. An immunopanel of p21, p27, and p53 could be useful for prognostication in colorectal carcinoma in addition to UICC stage. 相似文献