To the Editor: In the March 15, 2008, issue of Clinical Cancer Research, Sitnikova et al. (1) reported that IMP3 is an independent prognostic marker and can help predict disease progression in patients with superficial urothelial carcinomas of the bladder. Interestingly, over the past few years, IMP3 has been identified as an important biomarker for a number of other systemic malignancies besides urothelial carcinomas of the bladder.

IMP3 is an early biomarker of serous endometrial cancers. For instance, 94% of all serous endometrial carcinomas and 89% of all serous endometrial intraepithelial carcinoma are positive for IMP3 compared with 0% of endometrial intraepithelial neoplasia (2). IMP3 is also an early biomarker of adenocarcinoma in situ of the cervix. This has been confirmed by a recent study by Li et al. (3) who showed that 93% of adenocarcinoma in situ samples in their study were positive for IMP3. Similarly, IMP3 overexpression can distinguish malignant pancreatic lesions from benign pancreatic lesions (4). Increased IMP3 expression has also been reported in lung cancers. Studies by Jiang et al. (5) and, more recently, Hoffmann et al. (6) have also confirmed the clinical significance of IMP3 as a good prognostic biomarker for renal cell carcinomas. IMP3 also promotes tumor cell proliferation via an insulin-like growth factor II–dependent pathway (7) besides having a major influence on tumor cell invasion (8).

Suda et al. (9) have shown that an HLA-A24–restricted epitope, IMP-3-508, can induce a significant CTL response against IMP3 on lung cancer cells. Clearly, IMP3 seems to be rapidly emerging as a major biomarker and player in the etio-pathogenesis of multiple different systemic malignancies. Further studies are needed to identify other molecules that may reduce expression of IMP3 and thus help in the therapeutic management of malignancies such as renal cell carcinomas.

1
Sitnikova L, Mendese G, Liu Q, et al. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder.
Clin Cancer Res
2008
;
14
:
1701
–6.
2
Zheng W, Yi X, Fadare O, et al. The oncofetal protein IMP3: a novel biomarker for endometrial serous carcinoma.
Am J Surg Pathol
2008
;
32
:
304
–15.
3
Li C, Rock KL, Woda BA, Jiang Z, Fraire AE, Dresser K. IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16(INK4a) expression.
Mod Pathol
2007
;
20
:
242
–7.
4
Yantiss RK, Woda BA, Fanger GR, et al. KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas.
Am J Surg Pathol
2005
;
29
:
188
–95.
5
Jiang Z, Chu PG, Woda BA, et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study.
Lancet Oncol
2006
;
7
:
556
–64.
6
Hoffmann NE, Sheinin Y, Lohse CM, et al. External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma.
Cancer
2008
;
112
:
1471
–9.
7
Liao B, Hu Y, Herrick DJ, Brewer G. The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells.
J Biol Chem
2005
;
280
:
18517
–24.
8
Vikesaa J, Hansen TV, Jonson L, et al. RNA-binding IMPs promote cell adhesion and invadopodia formation.
EMBO J
2006
;
25
:
1456
–68.
9
Suda T, Tsunoda T, Daigo Y, Nakamura Y, Tahara H. Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy. Cancer Sci 2007.