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. 2009 Dec 10:9:430.
doi: 10.1186/1471-2407-9-430.

Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

Min Khine Maw  1 , Jiro Fujimoto, Teruhiko Tamaya
Affiliations

Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

Min Khine Maw et al. BMC Cancer. .

Abstract

Background: The inhibitor of DNA-binding (ID) has been involved in cell cycle regulation, apoptosis and angiogenesis. This prompted us to study ID functions in tumor advancement of ovarian cancers.

Methods: Sixty patients underwent surgery for ovarian cancers. In ovarian cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction. The histoscore with the localization of ID-1 was determined by immunohistochemistry. Patient prognosis was analyzed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD34 and factor VIII-related antigen.

Results: ID-1 histoscores and mRNA levels both significantly (p < 0.001) increased in ovarian cancers according to clinical stage, regardless of histopathological type. Furthermore, 30 patients with high ID-1 expression had a lower survival rate (53%) compared to patients with low ID-1 expression (80%). ID-1 histoscores and mRNA levels significantly (p < 0.0001) correlated with microvessel counts in ovarian cancers.

Conclusion: ID-1 increased in ovarian cancer cells during tumor progression. Moreover, ID-1 expression levels correlated with microvessel counts. Therefore, ID-1 might work on tumor advancement via angiogenesis and is considered to be a candidate for a prognostic indicator in ovarian cancers.

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Figures

Figure 1
Figure 1
ID-1, ID-2 and ID-3 mRNA levels in ovarian cancers classified according to clinical stage and histopathological type. Clinical staging of ovarian cancers was done according to FIGO. Each level is the mean ± SD of nine determinations. C, clear cell carcinoma; E, endometrioid adenocarcinoma; MCY, mucinous cystadenocarcinoma; SCY, serous cystadenocarcinoma, SPCY, serous papillary cystadenocarcinoma. Alive and deceased cases are numbered in open circles and closed circles, respectively. * p < 0.001.
Figure 2
Figure 2
Immunohistochemical staining for ID-1 with negative control in ovarian cancers. A representing case of clear cell carcinoma of the ovary. Rabbit anti-human ID-1 (SC-734, Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) was used at a dilution of 1:50 as the primary antibody. (original magnification ×400).
Figure 3
Figure 3
Correlation between ID-1 histoscores in cancer cells and mRNA (106 DNA copies/μg total RNA) levels in ovarian cancers. ID-1 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT-PCR, respectively. Each level is the mean ± SD of nine determinations.
Figure 4
Figure 4
ID-1 histoscores in ovarian cancers classified according to clinical stage and histopathological type. Clinical staging of ovarian cancers was done according to FIGO. Each level is the mean ± SD of nine determinations. C, clear cell carcinoma; E, endometrioid adenocarcinoma; MCY, mucinous cystadenocarcinoma; SCY, serous cystadenocarcinoma, SPCY, serous papillary cystadenocarcinoma. Alive and deceased cases are numbered in open circles and closed circles, respectively. * p < 0.001.
Figure 5
Figure 5
Survival rate after surgery for ovarian cancers. Patient prognosis was analyzed with a 36-month survival rate. High ID-1, cases with high histoscores and mRNA levels (> 160 histoscore and > 6.2 × 106copies/μg total RNA, respectively). Low ID-1, cases with low histoscores and mRNA levels (< 160 histoscore and < 6.2 × 106 copies/μg total RNA, respectively).
Figure 6
Figure 6
Correlation of ID-1 histoscores in cancer cells and mRNA levels in ovarian cancers with microvessel counts (MVCs). White circles, (MVC-CD34) by immunohistochemical staining for CD34; black circles, (MVC-FV-III) by immunohistochemical staining for factor VIII-related antigen. Each level is the mean ± SD of nine determinations.
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