Research Article: Clinical Significance of Amyloid Precursor Protein in Patients with Testicular Germ Cell Tumor

Date Published: April 14, 2013

Publisher: Hindawi Publishing Corporation

Author(s): Yuta Yamada, Tetsuya Fujimura, Satoru Takahashi, Kenichi Takayama, Tomohiko Urano, Taro Murata, Daisuke Obinata, Yasuyoshi Ouchi, Yukio Homma, Satoshi Inoue.


Introduction. The biological role of amyloid precursor protein (APP) is not well understood, especially in testicular germ cell tumors (TGCTs). Therefore, we aimed to investigate the immunoreactivity (IR) and expression of APP in TGCTs and evaluated its clinical relevance. Materials and Methods. We performed an analysis of immunohistochemistry and mRNA expression of APP in 64 testicular specimens and 21 snap-frozen samples obtained from 1985 to 2004. We then evaluated the association between APP expression and clinicopathological status in TGCTs. Results. Positive APP IR was observed in 9.8% (4/41) of seminomatous germ cell tumors (SGCTs) and 39.1% (9/23) of nonseminomatous germ cell tumors (NGCTs). NGCTs showed significantly more cases of positive IR (P = 0.00870) and a higher mRNA expression level compared with those of SGCTs (P = 0.0140). Positive APP IR was also significantly associated with α-fetoprotein (αFP) elevation (P = 0.00870) and venous invasion (P = 0.0414). Conclusion. We observed an elevated APP expression in TGCTs, especially in NGCTs. APP may be associated with a more aggressive cancer in TGCTs.

Partial Text

Testicular cancer is a relatively rare cancer that accounts for approximately 1–1.5% of male cancers, and 90–95% of these cancers are testicular germ cell tumors (TGCTs) [1]. TGCTs can be classified into two major histological categories, namely, seminomatous germ cell tumor (SGCT) and nonseminomatous germ cell tumor (NGCT). NGCTs, which include yolk sac tumors, embryonal cell carcinomas, teratomas, and choriocarcinomas, are different from SGCTs with regard to clinical characteristics and therapy required.

APP is ubiquitously expressed in various types of human cells. The extracellular domain of the APP has been suggested to be involved in transcellular adhesion [3] and neurite outgrowth [19, 20]. It may also function as a cell surface receptor [21, 22]. The intracellular domain of the APP is considered to be involved in cell migration [21, 23], cell signaling [4, 21], and apoptosis [21, 24, 25]. It also activates proliferation of epithelial cells [6]. These lines of evidence suggest that APP is involved in cancer cell proliferation. We have previously reported that APP contributes to androgen-dependent proliferation of prostate cancer cells and that the rate of cancer-specific survival for patients with APP-positive tumors was lower than that for patients with APP-negative tumors [14]. Another study revealed an APP overexpression in human pancreatic and colon cancer [13]. In the same study, small interfering RNA-mediated knockdown of APP also resulted in decreased cancer cell growth [13]. Involvement of APP expression is also suggested in cancer cells originating from the nasopharynx [8], oral cavity [9], thyroid [10, 11], and colon [12]. In a testicular germ cell tumor (TGCT), a recent study suggested an association of APP expression in transformed human pluripotent stem cells [26]. However, clinical significance of APP expression has not been evaluated. Therefore, we investigated the expression of APP in TGCTs and evaluated its association with clinical characteristics of TGCT.

The current findings show that APP levels are elevated in TGCTs, especially in NGCTs. APP elevation may indicate a more aggressive histological type of TGCTs.




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