An intrapelvic extraintestinal gastrointestinal stromal tumor of undetermined origin: diagnosis by prostate needle biopsy.

We herein report a case of intrapelvic gastrointestinal stromal tumor (GIST) of undetermined origin in a 48-year-old male who presented with dysuria. An enlarged tumor was detected on digital rectal examination. Imaging studies showed a solid and lobular homogenous tumor of 7.0 cm in diameter. The tumor was attached to the right dorsal aspect of the prostate with compression of the seminal vesicles and rectum. It was considered that the tumor had arisen from the prostate, although the patient's serum prostate-specific antigen level was low (0.436 ng/mL). The histological diagnosis by prostate needle biopsy was a spindle cell tumor. At cystoprostatectomy, the tumor was confirmed to be separated from the prostate by a fibrous band, and showed spindle cells with a fascicular growth pattern, but without necrotic areas. Mitotic figures were noted in 12 of 50 high-power fields. The tumor cells were immunoreactive for the KIT protein (CD117), CD34, Discovered on GIST-1 (DOG-1), and vimentin. In contrast, they were negative for desmin, α-smooth muscle actin, pancytokeratin (AE1/AE3), and S100 protein. The Ki-67 labeling index was 5%. The genetic analyses targeting the c-kit gene revealed a point mutation at codon 559 (GTT→GAT). The diagnosis of GIST was confirmed on the basis of the morphological features, immunoprofile, and results of the molecular analyses. Since extraintestinal GIST can resemble a prostatic tumor clinically, KIT (CD117) and DOG-1 should be considered for inclusion in the immunohistochemical panel for spindle cell tumors obtained by prostate needle biopsy.

Overexpression of HER2 signaling to WAVE2-Arp2/3 complex activates MMP-independent migration in breast cancer.

The final signal for triggering the formation of lamellipodia that initiate directional migration of mammalian cells is binding of the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2) to the actin-related protein 2 and 3 (Arp2/3) complex. This WAVE2-Arp2/3 signal is suggested to be enhanced in some breast cancers, facilitating invasion, and/or metastasis. Here, we demonstrated one cause of the enhanced signal using four breast cancer cell lines (SKBR3, AU565, MCF7, and MDA-MB-231). The WAVE2-Arp2/3 signal was estimated semi-quantitatively by counting the number of lamellipodia expressing both WAVE2 and Arp2 using high-power confocal laser microscopy. Higher expression of the WAVE2-Arp2/3 signal was detected in SKBR3 and AU565, which have HER2 gene amplification, than in the other two cell lines that lack HER2 gene amplification. Trastuzumab suppressed both the formation of lamellipodia and migration in a Boyden chamber experiment in SKBR3 and AU565. When the HER2 gene was transfected into MCF7, the number of both lamellipodia and migrated cells was increased. This enhancement of migration did not occur in the presence of extracellular matrix, and zymographic analysis showed no clear difference between HER2 gene-transfected cells and MCF7 cells. Immunohistochemical analysis of 115 cases of breast cancer revealed that coexpression of WAVE2 and Arp2 was significantly correlated with HER2-overexpression (P < 0.0001). These data indicate that an abnormal signal resulting from HER2 gene amplification activates lamellipodia formation in breast cancer cells, which initiates their metalloproteinase-independent migration.