Cancer Research and Treatment (2024)

The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer: Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha; Cancer Res Treat. 2019;51(4):1411-1419. Published online February 25, 2019; DOI: https://doi.org/10.4143/crt.2018.663

AbstractPDFSupplementary MaterialPubReaderePub

Purpose
We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC.
Materials and Methods
With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9- negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67– high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling.
Results
The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016).
Conclusion
This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Citations

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Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer
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CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer: Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Rock Bum Kim, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha; Cancer Res Treat. 2016;48(1):142-152. Published online March 17, 2015; DOI: https://doi.org/10.4143/crt.2014.227

AbstractPDFPubReaderePub

Purpose
The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer.
Materials and Methods
With various gastric tissues, we performed immunohistochemical staining for CD44v9.
Results
The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p = 0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-YSR in stage I, 81.7% vs 95.2%; p = 0.013), but not in AGC (5-YSR in stage II, 66.9% vs 62.2%; p = 0.821, 5-YSR in stage III, 34.5% vs 32.0%; p = 0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis.
Conclusion
This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.

Citations

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The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer
Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha
Cancer Research and Treatment.2019; 51(4): 1411.CrossRef
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A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer: Won Sup Lee, Gyeong-Won Lee, Hwal Woong Kim, Ok-Jae Lee, Young-Joon Lee, Gyung Hyuck Ko, Jong-Seok Lee, Joung Soon Jang, Woo Song Ha; Cancer Res Treat. 2005;37(4):208-211. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.208

AbstractPDFPubReaderePub

Purpose

Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer.

Materials and Methods

Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m²/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m²/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks.

Results

Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19~57%). The median response duration was 23 weeks (range: 4~60 weeks). The median time to progression was 26 weeks (range: 3~68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state.

Conclusion

This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.

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