Tzer-Ming Chen

Vascularity index as a novel parameter for the in vivo assessment of angiogenesis in patients with cervical carcinoma.

The importance of angiogenesis now is well recognized. Conventionally, tumor angiogenesis is assessed by determination of microvessel density (MVD) in the surgical specimen. This study examines tumor angiogenesis using power Doppler ultrasound and a quantitative image processing system. The authors hope to develop an in vivo and noninvasive method for quantitating tumor angiogenesis.

Incremental angiogenesis assessed by color doppler ultrasound in the tumorigenesis of ovarian neoplasms

Background. The crucial role of angiogenesis in tumor behavior has been studied extensively in vitro. The authors assessed the in vivo angiogenesis in ovarian neoplasms by color Doppler ultrasound and waveform analysis.

Vascular endothelial growth factor in cervical carcinoma

OBJECTIVE To quantitate vascular endothelial growth factor of cervical carcinoma and elucidate its clinical correlation. METHODS Intratumoral protein levels of vascular endothelial growth factor were measured in 104 cervical cancer patients and in 30 cervical tissue specimens of benign gynecologic diseases as controls. The concentrations were correlated with clinical and pathologic characteristics. RESULTS The median concentrations of vascular endothelial growth factor in cervical cancer tissues were higher than those in benign cervical tissues (180.0 versus 0.0 pg/mg of protein, P < .001). Tumors larger than 4 cm (1030.0 versus 118.0 pg/mg of protein, P < .001) and with deep stromal invasion (364.0 versus 111.0 pg/mg of protein, P = .016) had higher levels than those smaller than 4 cm or with superficial stromal invasion. Higher levels were also found in tumors with lymphovascular emboli (568.0 versus 118.0 pg/mg of protein, P = .006), parametrial invasion (582.0 versus 117.0 pg/mg of protein, P = .04), and pelvic lymph node metastasis (759.5 versus 121.0 pg/mg of protein, P = .002) than in those without. The protein levels of vascular endothelial growth factor correlated positively with tumor sizes (r = 0.340, P < .001). Tumors with overexpressed VEGF were larger (3.35 +/- 1.17 versus 2.13 +/- 1.28 cm, P < .001) and had higher incidence of deep stromal invasion (20 of 57 versus 6 of 47, P = .009), lymphovascular emboli (15 of 33 versus 11 of 71, P = .011), parametrial invasion (15 of 32 versus 11 of 72, P = .002), and lymph node metastasis (10 of 20 versus 16 of 84, P = .004). CONCLUSION Intratumoral protein level of vascular endothelial growth factor in cervical cancer tissue correlates well with local tumor progression and tumor metastasis. Vascular endothelial growth factor might be a marker for evaluating disease severity.

Clinical application of intratumoral blood flow study in patients with endometrial carcinoma

The objective of this study was to evaluate the correlation between intratumoral blood flow as assessed by color Doppler ultrasound with stage, tumor grade, depth of invasion, and lymph node metastasis in endometrial carcinoma and determine its clinical usefulness.

Vascular patterns of gestational trophoblastic tumors by color doppler ultrasound

Background. Destruction of uterine vasculature is a common phenomenon in gestational trophoblastic tumors. The authors categorized such uterine vasculature by color Doppler ultrasound and studied its clinical significance.

Endometrial stromal sarcoma of twenty cases.

Background. Endometrial stromal sarcoma is a rare neoplasm. We reviewed twenty cases to study the characteristics of this disease.

Correlation of Uterine Hemodynamics With Chemotherapy Response in Gestational Trophoblastic Tumors

Objective: To assess the uterine hemodynamics in gestational trophoblastic tumors and to correlate them with response to chemotherapy. Methods: Using transvaginal color Doppler ultrasound, we measured the peak systolic velocity and the resistance index (RI) of the uterine arteries in 23 women with gestational trophoblastic tumors before each course of chemotherapy. Fifty‐five nonpregnant women and another 15 women who had uneventful molar evacuation were enrolled as controls. Two‐tailed Student t test was used for statistical analysis. Results: A hyperdynamic uterine circulation was noticed at diagnosis in all gestational trophoblastic tumors, manifested as higher peak systolic velocity (mean ± standard deviation 57.5 ± 20.4 cm/second) of the uterine arteries compared to nonpregnant (28.3 ± 3.41 cm/second; P < .0001) and uneventful post‐mole uteri (26.8 ± 3.08 cm/second; P < .0001). The RI values of the uterine arteries in gestational trophoblastic tumors at diagnosis ranged from 0.21‐0.80. However, the mean value (0.56 ± 0.19) was lower than those of nonpregnant (0.80 ± 0.05; P < .0001) and post‐mole uteri (0.75 ± 0.06; P < .0001). A higher pre‐treatment uterine artery RI (mean 0.71 ± 0.09) was noted in ten patients with gestational trophoblastic tumors requiring fewer than five courses of chemotherapy, compared with the mean in 13 patients requiring longer courses of treatment (0.47 ± 0.14; P < .0001). There was a marked decrease of peak systolic velocity during the first three courses of treatment in the former group (54.2 to 23.6 cm/second; P < .001), in contrast to no change in the latter group (60.1 to 60.5 cm/second). Conclusion: Uterine hemodynamic characteristics assessed by color Doppler ultrasound might predict and monitor the response to chemotherapy in gestational trophoblastic tumors. (Obstet Gynecol 1994;83:1021‐5)

Coexistence of human cytomegalovirus and human papillomavirus type 16 correlates with lymph node metastasis in cervical cancer

Human papillomaviruses (HPV), and human cytomegalovirus (HCMV) have been associated with cervical carcinogenesis. To our knowledge, there has been no report on the role of HCMV in the clinical behavior of cervical cancer. We recently reported that the presence of HPV DNA correlated with a higher incidence of lymph node metastasis, and we now report on whether or not HCMV DNA was present in those 433 cervical carcinomas; 113 cases (26.3%) were confirmed to contain HCMV DNA. HCMV+/HPV+ patients but not HCMV−/HPV+ patients had a significantly higher rate of metastasis to the lymph nodes, compared to HCMV−/HPV− cases (27/92, 29.3% compared to 8/70, 11.4%,P<0.025). Interestingly, the synergistic effects of HCMV and HPV only existed in cervical carcinomas with HPV type 16, and not in those with other HPV genotypes. Only in HPV16+ cases did the presence of HCMV in tumors enhance lymph node metastasis (17/48 compared to 30/152,P<0.05). The results underline the prognostic significance of HCMV in HPV16+ cervical cancer.

Establishment and characterization of a human-papillomavirus negative, p53-mutation negative human cervical cancer cell line

A human cervical cancer cell line, CX, was established from a patient with squamous cell carcinoma of the uterine cervix. The CX cells were epithelial in morphology with relatively large vesicular nuclei, and prominent nucleoli. Cytoplasmic organelles were generally sparse but tonofilaments were relatively abundant. The cells grew as a compact sheet with close membrane approximation interconnected by desmosome-like junctions. CX cells contained cytokeratin, but not vimentin. Elevated levels of squamous cell carcinoma antigen and carcinoembryonic antigen were detected in the cell supernatants. Population doubling time was estimated to be about 20 h. CX cells were not able to grow in soft agar and not tumorigenic in nude mice. Chromosome analysis revealed that CX cells were heterogeneous and mainly had a female diploid karyotype. Unlike cervical cancer cell lines published previously, CX cells were demonstrated to be human papillomavirus-negative, p53 mutation-negative. Based on the distinct characteristics, CX cell line may prove to be a useful tool for the study of human cervical carcinogenesis.

Human papillomavirus DNA and p53 status in stage IB bulky cervical cancer.

SummaryWe used the polymerase chain reaction (PCR) to study the presence and typing of human papillomavirus (HPV) DNA, and PCR/single-strand confirmation polymorphism to survey the mutations of the p53 gene in exons 5–9 in 26 bulky stage IB cervical cancers. The HPV DNA was present in 20 out of the 21 (95%) squamous-cell carcinoma tissues, including 13 cases of HPV-16, 0 case of HPV-18, and 7 cases of other HPV types. In the other 5 adenocarcinoma tissues, 3 had HPV type-18 DNA and 2 had no detectable HPV DNA. The distribution of HPV DNA in bulky tumors was not statistically different from that in the other 228 squamous-cell carcinomas and 23 adencarcinomas of smaller size operated upon during the same period. Out of the 26 patients, 9 (35%) had lymph node metastasis at the time of operation. During the follow-up period ranging from 19 to 48 months, 9 patients had recurrence and 7 of them died of disease. The distribution of HPV types was not related to the prognosis in these patients. There were no p53 mutations detected in all the 26 samples. Thus, HPV type and the status of p53 could not serve as additional prognostic factors in stage IB bulky cervical cancers.