Increased proliferative activity caused by loss of p21<sup>WAF1/CIP1</sup> expression and its clinical significance in patients with early‐stage gastric carcinoma

Noda, Hiroshi; Maehara, Yoshihiko; Irie, Koji; Kakeji, Yoshihiro; Yonemura, Tomohiro; Sugimachi, Keizō

doi:10.1002/cncr.10417

Cited by 16 publications

(11 citation statements)

References 28 publications

(35 reference statements)

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“…Other clinicopathological factors, including lymph node involvement and depth of invasion have not been found to correlate with Ki-67 index [18,19]. Like other researchers [2,[19][20][21][22][23], we found a statistically significant correlation of Ki-67, PCNA and MCM2 PI in advanced gastric cancer with local lymph node involvement. The mean proliferation indices for Ki-67 and PCNA were higher in gastric cancer with local lymph node involvement.…”

Section: Discussionsupporting

confidence: 59%

“…Patients with high PCNA PI in early gastric carcinoma much more frequently have lymph node metastases. Moreover, the postoperative survival time of patients with high PCNA PI in gastric carcinoma is considerably shorter than in the case of low PCNA PI in tumour tissue [23,25]. Mûller et al [15] observed no difference in the length of postoperative survival between patients with low and high Ki-67 index.…”

Section: Discussionmentioning

confidence: 98%

“…Our data are consistent with those published by Aoyagi et al [25], who observed a significant correlation of PCNA PI with depth of invasion, histological differentiation and the clinical stadium of the disease, thus stating that PCNA index is a good prognostic factor in gastric cancers. Many investigators have found Ki-67 and PCNA to be prognostic factors in tumours of the stomach [13][14][15]22,23,[26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

Czyżewska

Guzińska‐Ustymowicz²,

Pryczynicz³

et al. 2009

Folia Histochem Cytobiol.

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Abstract:The current study objective was to assess the proliferation indices (PI) of Ki-67, PCNA and MCM2 proteins in advanced gastric cancer and in metastatic lymph node in correlation with certain clinicopathological features and with postoperative survival of patients. The study was conducted in a group of 100 patients with advanced gastric cancers. Involvement of local lymph nodes was present in 36 cases. Immunohistochemical investigations were carried out using monoclonal antibodies against Ki-67 (DAKO), PCNA (DAKO) and polyclonal antibody to MCM2 (Santa Cruz Biotechnology). Visualization of the antigen/antibody complex was performed using LSAB technique (biotin-streptavidin-peroxidase) followed by application of chromogene DAB (DAKO). Statistical analysis revealed no correlations of Ki-67, PCNA and MCM2 PI in tumour tissue or metastatic lymph node with patients' age and gender, tumour location, histological grade, macroscopic type according to Bormann's classification and histological grading by Lauren's and Goseki's classifications. Moreover, no correlation was observed of Ki-67 and MCM2 PI in tumour tissue with histological grading. No correlation was also noted between the proliferation indices of all the three proteins in the affected lymph node and grade of histological differentiation. Such clinicopathological parameters as patients' age and gender, histological grading by Lauren's and Goseki's classifications and lymph node involvement did not correlate with survival time of patients. Furthermore, no statistically significant correlation was shown of postoperative survival time with Ki-67 and MCM2 PI in tumour tissue and metastatic lymph nodes and with PCNA PI in the affected lymph nodes. However, a statistically significant correlation was found of Ki-67, PCNA and MCM2 PI in tumour tissue and metastatic lymph nodes with depth of wall invasion and local lymph node involvement. A statistically significant correlation was also noted between PCNA PI in the main mass of tumour and histological grading. The postoperative survival time of patients exhibited a statistically significant correlation with tumour location and macroscopic type according to Bormann's classification. Correlations on statistical borderline were noted between survival time and depth of gastric wall invasion and PCNA PI in the main mass of tumour.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

Czyżewska

Guzińska‐Ustymowicz²,

Pryczynicz³

et al. 2009

Folia Histochem Cytobiol.

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“…None of the gastric carcinomas with negative immunoreaction for p21 waf1 exhibited lymph node metastasis, and there was a higher frequency of lymph node involvement in cases with greater positivity for p21 waf1 , as previously documented (17,25). It was observed that 65.4% of the cases were positive for p21 waf1 , and a higher incidence of lymph node involvement was also found in patients with increased proliferative activity and loss of expression of p21 waf1 in tumor tissue (26).…”

Section: Kip1supporting

confidence: 77%

Characterization of oncogene suppressor marker expression in patients with submucosal gastric carcinoma

et al. 2017

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Abstract.wafl/cip1 was positive in 32.4, 72.7 and 71.4% of the cases, respectively. All the tumors were positive for p53. Tumors with lymph node invasion presented with overexpression (+4) of p53 in 47% of the cases vs. 17% of patients who did not have lymph node involvement. Therefore, higher expression of p53, p21 ras and p21 wafl/cip1 in the tumor exhibited a statistically significant association with lymph node involvement.

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“…44 However, low p21 Waf/Cip1 and p27 Kip1 expressions have been reported in gastric cancers and related cancer progression. 45,46 Activation of the MAPK and NFjB pathway is associated with gastric cancers and development. 47,48 Therefore, increased Id-1 expression may contribute to gastric cancer development by regulating these signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Id-1gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer

2005

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The molecular mechanisms underlying the chemopreventive effects of NSAIDs are not well understood and remain the subject of debate. One of the mechanistic possibilities involves alterations in gene expression. We examined gene expression profiles in SNU601 gastric cancer cells treated with sulindac sulfide (50 lM) for 24 hr. Microarray analysis showed that 1.3% (105/8170) of genes were induced or repressed more than 3-fold in cells treated with sulindac sulfide. Seven genes were selected and confirmed by reverse transcription-polymerase chain reaction. Inhibitor of differentiation/DNA binding-1 (Id-1) was downregulated in SNU601 cells treated with sulindac sulfide. Id-1 expression level was decreased dose-dependently by sulindac sulfide. In addition, the expression pattern of Id-1 was inversely related to that of nm23. We also examined Id-1 expression in human gastric cancer tissues and compared it with clinicopathologic parameters to study its biologic role in the cancers. Id-1 was frequently and strongly expressed in gastric cancer tissues compared with that in adjacent nonmetaplastic mucosa. Its immunoreactivity scores were positively correlated to Ki67 labeling indices and tumor progression, and is higher in intestinal type than in diffuse type. In summary, a number of genes, both induced and repressed, could be important in mediating sulindac sulfide-induced cell death in gastric cancer cells. Id-1, one of the repressed genes, is upregulated in gastric cancers and has positive role in tumor progression and histogenesis of intestinal-type cancers. ' 2005 Wiley-Liss, Inc.

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Increased proliferative activity caused by loss of p21^WAF1/CIP1 expression and its clinical significance in patients with early‐stage gastric carcinoma

Cited by 16 publications

References 28 publications

Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

Characterization of oncogene suppressor marker expression in patients with submucosal gastric carcinoma

Id-1gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer

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Increased proliferative activity caused by loss of p21WAF1/CIP1 expression and its clinical significance in patients with early‐stage gastric carcinoma

Cited by 16 publications

References 28 publications

Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer.

Characterization of oncogene suppressor marker expression in patients with submucosal gastric carcinoma

Id-1gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer

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Increased proliferative activity caused by loss of p21^WAF1/CIP1 expression and its clinical significance in patients with early‐stage gastric carcinoma