Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients

Myoung, Hoon; Kim, M.-J.; Lee, J.-H.; Ok, Yong-Ju; Paeng, Jun-Young; Yun, Pil‐Young

doi:10.1016/j.ijom.2006.07.016

Cited by 82 publications

(75 citation statements)

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“…This heterogeneous result showed the correlation of Ki-67 expression to tumor phenotype factors. However, there is a correlation of Ki-67 expression for lymph node status (Myoung et al, 2006), whereas other studies reported no statistical association between Ki-67 expression and tumor phenotype factors (Bettendorf and Herrmann, 2002). Thus, Ki-67 seems to have no distinct meaning as a marker for head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 89%

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G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

Zhang¹,

Xu²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.

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Section: Discussionmentioning

confidence: 89%

“…Several researches have focused on the significance of Ki-67 in squamous cell carcinoma of head and neck (Girod et al, 1998;Sittel et al, 1999;Stoll et al, 2000;Bettendorf and Herrmann, 2002;Carinci et al, 2002;Myoung et al, 2006). This heterogeneous result showed the correlation of Ki-67 expression to tumor phenotype factors.…”

Section: Discussionmentioning

confidence: 96%

G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

Zhang¹,

Xu²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Ki-67 expression did not correlate with overall survival in any other stage, possibly because Ki-67 expression below 33% was generally observed in only stage I OTSCC. Other studies in oral cancer investigating the correlation between Ki-67 expression and overall survival in patients found conflicting results although several studies confirmed that a lower Ki-67 expression exhibited better patient survival (Gonzalez-Moles et al, 1996;Piffko et al, 1996;Stoll et al, 2000;Myoung et al, 2006;Kim et al, 2007). One study by Kim et al (2007) observed a significantly longer patient survival when Ki-67 expression was below 10% in OTSCC patients.…”

Section: Discussionmentioning

confidence: 99%

Ki-67 expression predicts locoregional recurrence in stage I oral tongue carcinoma

et al. 2008

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Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer associated with poor prognosis. Methods for determining the aggressiveness of OTSCC from analysis of the primary tumour specimen are thus highly desirable. We investigated whether genomic instability and proliferative activity (by means of Ki-67 activity) could be of clinical use for prediction of locoregional recurrence in 76 pretreatment OTSCC paraffin samples (stage I, n ¼ 22; stage II, n ¼ 33; stage III, n ¼ 8; stage IV, n ¼ 13). Eleven surgical tumour specimens were also analysed for remnants of proliferative activity after preoperative radiotherapy. Ninety-seven percent of cases (n ¼ 72) were characterised as being aneuploid as measured by means of image cytometry. Preoperative radiotherapy (50 -68 Gy) resulted in significant reduction of proliferative activity in all patients for which post-treatment biopsies were available (P-value ¼ 0.001). Proliferative activity was not associated with response to radiation in stage II patients. However, we report a significant correlation between high proliferation rates and locoregional recurrences in stage I OTSCC patients (P-value ¼ 0.028). High-proliferative activity is thus related to an elevated risk of recurrence after surgery alone. We therefore conclude that Ki-67 expression level is a potentially useful clinical marker for predicting recurrence in surgically treated stage I OTSCC.

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“…Particularly, the expression levels of known representative cell proliferation markers such as PCNA, Ki-67, EGFR, and survivin [33][34][35][36] were down-regulated by rPK1-3 treatment. The over-expression of these proteins might be related to tumor aggressiveness and poor prognosis of several malignant tumors [36][37][38]. In addition, tumor suppressor proteins such as p53, p21, and RB-1 [39][40][41] were down-regulated by rPK1-3, thus inducing tumor cell apoptosis and cell cycle suppression.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effect of recombinant plasminogen kringle 1–3 in KB cells: Histological observation and immunoprecipitation-based high performance liquid chromatography

Lee

朴瑛郁²,

Lee

et al. 2017

Oral Biol Res

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·············································································································································································Angiostatin containing plasminogen kringle 1-4 domain is an endogenous angiogenesis inhibitor with anti-tumor effect. The present study applied recombinant human plasminogen kringle 1-3 (rPK1-3) in KB cell culture and BALB/c-nude mice, to elucidate the in vitro and in vivo anti-tumorigenic effect. Nude mice (n = 4) treated with rPK1-3, were compared to cisplatin treated nude mice (n = 4) and saline controls (n = 2). In vitro, the KB cells were also exposed to 10 μM of rPK1-3 for 12 and 24 hours. Cells were evaluated histologically, and their protein expression was analyzed by immunoprecipitation-based high performance liquid chromatography (IP-HPLC). Results revealed that rPK1-3 potently inhibited the growth of KB cells in cell culture, but not in animal study. The KB cells treated with rPK1-3 showed growth arrest with decreased expression of PCNA, Ki-67, and MPM2, but enhanced apoptosis and increased expression of p53, BID, BAK, BAX, and caspase 9. Reduced cellular adaptation was also observed, with decreased expression of TGF-β1, SMAD4, pAKT, mTOR, EGFR, and PKC. Anti-angiogenesis effects with decreased expression of VEGF-A, VEGFR, angiogenin, vWF, LYVE-1, D2-40, CD31, MMP-2, and bFGF were also observed in cells treated with rPK1-3. These results suggest that in vitro, rPK1-3 has potent antitumorigenic effects, such as growth inhibition, increased apoptosis, reduced cellular survival, and tumor anti-angiogenesis. Therefore, rPK1-3 can be used as an anti-tumor agent for tumor cells in the absence of host systemic responses, including antibody formation.

show abstract

Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients

Cited by 82 publications

References 20 publications

G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

Ki-67 expression predicts locoregional recurrence in stage I oral tongue carcinoma

Anti-tumor effect of recombinant plasminogen kringle 1–3 in KB cells: Histological observation and immunoprecipitation-based high performance liquid chromatography

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