To study the sonographic evolution of hepatocellular carcinoma (HCC) in its early stage, 26 HCCs in 24 patients were observed regularly with real-time ultrasound for a period of 90 to 691 days. In the beginning, 21 tumors were hypoechoic, two isoechoic, and three diffusely hyperechoic. On follow-up, two of the 21 initially hypoechoic HCCs remained the same echodensity, 12 increased in internal echoes but were still hypoechoic, one became isoechoic, four changed to hyperechoic, and the remaining two shifted from hypoechoic to isoechoic and then to hyperechoic. The two initially isoechoic HCCs also gained echogenicity and became hyperechoic. By contrast, the three initially hyperechoic HCCs kept the same echo patterns. The "acquired" hyperechoic HCCs were inhomogeneous in echodensity and larger in size whereas the three originally hyperechoic HCCs were homogeneous and smaller. It is concluded that most small HCCs evolve progressively from hypoechoic to isoechoic and then to inhomogeneously hyperechoic patterns as they grow; a few HCCs have diffusely high echogenicity from the beginning and retain the same features thereafter.

The epidemiologic characteristics of lung cancer in Taiwan differ from those in other parts of the world in low male-to-female ratio, the high percentage of adenocarcinoma, and the relatively high percentage of nonsmokers who are victims. To investigate possible correlation between p53 gene alteration and the unique characteristics of lung cancer here, p53 gene status of 36 patients with primary, resected non-small-cell lung cancer (NSCLC) was studied by directly sequencing the cDNA of the p53 gene, then acquiring clinical and pathologic data to correlate p53 gene status with clinical parameters and pathologic staging. Missense mutations were present in 42% (15 of 36) of patients with NSCLC, including 42% (10 of 24) with adenocarcinomas, and 45% (five of 11) with squamous cell carcinomas. The frequency of p53 mutation was 50% in smokers and 29% in nonsmokers (p = 0.355). The mutation occurred most frequently in exon 8 (56%), and G:C to A:T transitions in non-CpG or CpG sites were the most commonly observed base changes (56%). These findings differ from the high prevalence of G to T transversion found in previous reports. The frequency of metastasis in hilar and mediastinal lymph nodes was significantly higher in tumors with p53 mutations. The association with nodal stage was strong for mutations within exon 8, but it was less apparent for mutations in other exons probably because of the small number. This study suggests that p53 gene missense is common in NSCLC in Taiwan, but smoking is probably not the sole contributing factor. More interestingly, p53 gene mutations, especially those in exon 8, may be associated with regional nodal metastasis.

Deletions of 5p15.33 (33.3%) and 16q12.2 (33.3%) are the most frequent hepatoblastoma-related events in our patient group with 5p15.33 microdeletion as a potential biomarker for the fate of survival with native liver.

Computer analysis of protein phosphorylation site sequences revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of proline-directed protein kinase F(A)/glycogen synthase kinase-3alpha (PDPK F(A)/GSK-3alpha) has been optimized to demonstrate significantly increased (p < 0.01) activity in poorly differentiated human prostate carcinoma PC-3 cells (55.5+/-3.8 units/mg) when compared to well-differentiated LNCaP cells (28.1+/-2.3 units/mg). Immunoblotting analysis revealed that increased activity of this PDPK in PC-3 cells is due not to overexpression of the protein, but to enhanced tyrosine phosphorylation of the kinase. When treated with genistein (a protein tyrosine kinase PTK inhibitor), the enhanced tyrosine phosphorylation/activation of the kinase in PC-3 cells can be blocked. Conversely, when treated with vanadate (a protein tyrosine phosphatase PTP inhibitor), the phosphotyrosine content of PDPK F(A)/GSK-3alpha in LNCaP cells can be promoted to the level of PC-3 cells. In sharp contrast, the PTK inhibitor has little effect on the tyrosine phosphorylation level of the kinase in LNCaP cells, whereas the PTP inhibitor has little effect on the tyrosine phosphorylation level of the kinase in PC-3 cells. Taken together, the results provide initial evidence that the tyrosine phosphorylation/activation levels of this oncogenic PDPK can be differentially regulated in well- and poorly differentiated prostate carcinoma cells.

MYST4 is a member of histone acetyltransferases which are involved in transcriptional activation of genes important for cellular growth and development. Our previous study revealed that overexpression of MYST4 in ovarian high-grade serous carcinoma correlated with worse survival. To further explore the role of MYST4 in human cancers, we selected hepatoma cell line Huh 7 due to its high level of MYST4 expression among various cancer cell lines tested. Immunohistochemical study showed that overexpression of MYST4 correlated with worse overall survival in hepatoceullular carcinoma (P = 0.02). Furthermore, tumor cells at invasion front and in lymphovascular spaces are frequently overexpressed. Knockdown of MYST4 in Huh 7 resulted in significantly reduced cellular growth, migration and perturbed cell cycle progression. Mouse xenograft model revealed that MYST4-knockdown Huh 7 cells had lower growth rate, consistent with the in vitro findings. Together, our studies suggest that MYST4 promotes cell growth, migration and lymphovascular spread in hepatocellular carcinoma. Thus, MYST4 may serve as a druggable target in treating hepatocellular carcinoma. Citation Format: Tsui Lien Mao, Jinn-Chyuan Sheu. Overexpression of MYST4 induces tumor progression in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5034.