Extragastrointestinal stromal tumor (EGIST) is a unique tumor that occurs outside the gastrointestinal tract. EGIST shows a c-kit expression and histologic appearance similar to those of gastrointestinal stromal tumor (GIST). Most GISTs have gain-of-functional mutation of the c-kit gene, and some have mutation of the platelet-derived growth factor receptor-alpha (PDGFRA) gene. However, the frequency of mutation of those genes in EGISTs remains unclear. We examined the clinicopathologic features, prognostic factors, and c-kit and PDGFRA mutation in 39 cases of EGIST. Tumors with high mitotic counts (>or=5/50 high power fields) or a high Ki-67 labeling index (>or=10%) were significantly correlated with worse prognoses. The c-kit mutation was found in the juxtamembrane domain (exon 11) and the extracellular domain (exon 9) in 12 of 29 cases (41.4%) and 2 of 29 cases (6.9%), respectively. The PDGFRA gene mutation was found at the juxtamembrane domain (exon 12) and the tyrosine kinase domain (exon 18) in one case each. The pattern of kit and PDGFRA mutation in EGIST was essentially similar to that in GIST. Our results suggest that the c-kit and PDGFRA mutations play an important role in the tumorigenesis of EGIST. High mitotic counts and a high Ki-67 labeling index may be useful for predicting the aggressive biologic behavior in EGIST. Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases.
Abstract. Histone deacetylase (HDAC) activity is one of the widely used and well-established mechanisms for regulation of various genes in cancer. To identify which subtype of class I HDACs are overexpressed in cancers, we analyzed the expression of class I HDAC isotypes composed of HDAC1, 2, 3 and 8 in several cell lines and human cancer tissues, including cancer of the stomach, esophagus, colon, prostate, breast, ovary, lung, pancreas and thyroid. The results showed that >75% of human cancer tissues and their corresponding non-cancerous epithelium showed high expression of these class I HDACs. However, the immunoreactivity of HDAC8 in both prostatic cancer tissue and non-cancerous prostate glands was lower than that in other cancer tissues. Furthermore, 5-40% of cancer tissues overexpressed class I HDACs, when compared with normal epithelium. The results suggest the potential usefulness of HDAC inhibitors for the treatment of a wide variety of human cancers.
Purpose: To evaluate the usefulness of apparent diŠusion coe‹cient (ADC) for the diŠerential diagnosis of breast tumors and to determine the relation between ADC and tumor cellularity.Materials and Methods: One hundred and thirty-six female patients (age range, 17-83 years; average age, 51.7 years) with 140 histologically proven breast tumors underwent diŠusion-weighted magnetic resonance (MR) imaging (DWI) using the spin-echo echo-planar technique, and the ADCs of the tumors were calculated using 3 diŠerent b values, 0, 500, and 1000 s/mm 2 . The diagnoses consisted ofˆbroadenoma (FA, n=16), invasive ductal carcinoma, not otherwise speciˆed (IDC, n=117), medullary carcinoma (ME, n=3) and mucinous carcinoma (MU, n=4). Tumor cellularity was calculated from surgical specimens. The ADCs of breast tumors and cellularity were compared between diŠerent histological types by analysis of variance and ScheŠe's post hoc test. The correlation between tumor cellularity and ADC was analyzed by Pearson correlation test.Results: Signiˆcant diŠerences were observed in ADCs between FA and all types of cancers (Pº0.05) and between MU and other types of cancers (Pº0.01) and in cellularity between FA and cancers except MU (Pº0.01) and between MU and other types of cancers (Pº0.01). There was an inverse correlation between ADC and tumor cellularity (Pº0.01, r 2 =0.451).Conclusions: The ADC may potentially help in diŠerentiating benign and malignant breast tumors. Tumor ADC correlates inversely with tumor cellularity.
A persistent or flat TIC pattern on dynamic contrast-enhanced MR images indicates benign disease, but there is added value from including the ADC value in the evaluation of tumors that show a plateau or washout TIC pattern.
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