Chien-Hsing Lu

KAI1 Metastasis Suppressor Gene Is Frequently Down-Regulated in Cervical Carcinoma

KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. It belongs to a structurally distinct family of cell surface glycoproteins. Decreased KAI1 expression has been observed in several common solid epithelial tumors, including prostatic, pancreatic, lung, hepatic, colorectal, ovarian, and esophageal cancers. A recent study also observed frequent loss of KAI1 expression in a number of squamous cell carcinomas of the cervix by immunohistochemical technique. To further confirm whether this gene is altered in this malignancy, we analyzed KAI1 expression in various stages of cervical carcinoma by a molecular method. Total cellular RNA was extracted from 84 primary invasive cervical carcinomas and 6 metastatic or recurrent lesions. cDNA was synthesized and was used for real-time quantitative polymerase chain reaction analysis. The level of KAI1 expression was obtained as the value of threshold cycle (Ct) and was quantitated with a comparative Ct method. In addition, paraffin blocks of the tumors were selected and prepared for immunohistochemical study with an anti-KAI1 polyclonal antibody, C-16. Both the real-time quantitative polymerase chain reaction method and immunohistochemical study revealed a frequent decrease in KAI1 expression in invasive cervical cancers and metastatic or recurrent lesions. However, the reduction in KAI1 was not related to progression of the disease. When tumor cell differentiation was analyzed, poorly differentiated tumors showed a greater decrease in KAI1 expression than well or moderately differentiated tumors (P < 0.001). Histologically, KAI1 loss was observed equally in both squamous cell carcinoma and adeno-/adenosquamous carcinoma. Since down-regulation of KAI1 occurs in both early and late stages of cervical cancer, we suggest that its involvement in the progression of this malignancy is an early event.

Prediction of persistence or recurrence after conization for cervical intraepithelial neoplasia III.

OBJECTIVE: To estimate the predictive factors for persistent/recurrent disease before and after conization for cervical intraepithelial neoplasia III. METHODS: Patients who received conization due to histologic diagnosis of cervical intraepithelial neoplasia III from 1998 to 2000 and who had at least one cytologic/histologic follow-up within one year of conization (n = 449) were enrolled in our study. All available demographic and pathologic parameters were analyzed. RESULTS: We performed multivariable logistic regression analysis to identify predictive factors for cervical intraepithelial neoplasia III persistence/recurrence. Age (greater than 50 years) was the only preoperative predictor and had an odds ratio equaling 3.070 (95% confidence interval [CI] 1.421–6.630, P = .004). Post–cone endocervical curettage was found to be the most statistically significant factor for predicting persistent disease (odds ratio 7.940, 95% CI 3.428–18.390, P < .001). Positive endocervical curettage was associated with 65.5% (36/55) of persistent disease, whereas negative endocervical curettage was associated with only 7.6% (26/342). Positive endocervical resection margins and multiple-quadrant disease also had predictive values with odds ratios equaling 2.972 (95% CI 1.401–6.281, P = .004) and 2.180 (95% CI 1.014–4.689, P = .046), respectively. The positive predictive values for age (> 50 years), positive endocervical curettage, positive endocervical resection margin, and multiple quadrant disease were 31.7%, 65.5%, 40.0%, and 21.9%, respectively. CONCLUSION: We found that age is the only preoperative predictive factor. Pathologic parameters, including endocervical curettage, endocervical resection margins, and multiple-quadrant disease are the only postoperative predictive factors for cervical intraepithelial neoplasia persistence or recurrence found in our study. These factors should be considered in patient management before and after therapeutic conization for cervical intraepithelial neoplasia III. LEVEL OF EVIDENCE: II-3

Should Adequacy Criteria in Cervicovaginal Cytology Be Modified After Radiotherapy, Chemotherapy, or Hysterectomy?

The general criterion of an unsatisfactory Papanicolaou (Pap) test in the 2001 version of the Bethesda system is not applicable to patients after treatment with radiotherapy, chemotherapy, or hysterectomy. The current study was performed to determine whether specimen adequacy criteria for Pap tests should be modified for these conditions.

Expression Analysis of Apoptosis-related Markers TP53, BCL-2, BAX and c-MYC in Female Genital Tract Sarcomas

Background: Most female genital tract sarcomas are highly malignant and fatal. Their aggressive growth pattern and poor response to chemotherapy are the major causes of death. Deregulation of the apoptosis pathway is related to tumorigenesis and chemodrug resistance. The purpose of this study was to investigate the expression status and relationship of the apoptosis‐related markers TP53, BCL‐2, BAX and c‐MYC in this group of tumors. In addition, correlations of these markers with clinicopathologic findings and their prognostic significance were also examined. Methods: Paraffin blocks of female genital tract sarcoma tissue from 54 patients were obtained after pathology review. Protein expression of TP53, BCL‐2, BAX and c‐MYC was examined using immunohistochemical staining with standard procedures. A semiquantitative method was used to assess the staining result where scoring 1–3 was negative and 4–9 was positive for expression. The mutual relationships between TP53, BCL‐2, BAX and c‐MYC were examined. Associations between expression of the apoptotic markers and tumor stage as well as outcome were also analyzed. Results: We found that all 4 of the apoptosis‐related markers were frequently expressed in female genital tract sarcomas. Of the 54 cases, 24 (44%) were positive for TP53, 23 (43%) for BCL‐2, 25 (46%) for BAX, and 30 (56%) for c‐MYC. A significant positive association was observed between BAX and c‐MYC (p < 0.001). There was no significant difference for the expression status of the 4 markers in early and late stage tumors. In prognostic analysis, overexpression of TP53, late stage, and age were significant prognostic factors in both univariate and multivariate analyses. Conclusion: Since changes in TP53, BCL‐2, BAX and c‐MYC frequently occur in female genital tract sarcomas, deregulation of apoptosis appears to be involved in the pathogenesis of this group of tumors. This mechanism may occur early in tumorigenesis and include the c‐MYC/BAX apoptotic pathway or BCL‐2. However, TP53 mutation may play a crucial role in this process, and clinically, it could be used as a prognostic indicator.

Loss of Smad4 protein expression occurs infrequently in endometrial carcinomas

Smad4 is a member of the Smad proteins, which are needed for mediating signals of transforming growth factor &bgr; from the cell surface to the nucleus. Smad4 is also a tumor suppressor gene for cancers of the pancreas, colon, and lung. The aim of this study was to investigate the expression and prognostic significance of this gene product in endometrial cancer. Immunohistochemical staining for Smad4 was performed on formalin-fixed, paraffin-embedded specimens of endometrial tumors with an anti-Smad4 monoclonal antibody (clone B8): 97 primary endometrial carcinomas, 20 cases of endometrial hyperplasia, and 26 cases of metastases from endometrial carcinoma. The immunoreactivity of each tumor was correlated with the clinical and histopathologic parameters of the patients. Diffusely positive expression of Smad4 protein was detected in all 20 cases of endometrial hyperplasia and in most of the primary and metastatic endometrial cancers. The frequency of positive expression decreased progressively with tumor grade. Clinically, however, it was not associated with tumor progression, nor did it predict patient outcome. Although loss of heterozygosity at chromosome 18q21 (the location of the Smad4 gene) is frequent in endometrial carcinomas, the authors show in this immunohistochemical study that inactivation of this gene occurs infrequently in this tumor.

Report of two cases of adenoid cystic carcinoma of Bartholin's gland and review of literature.

OBJECTIVE Primary adenoid cystic carcinoma (ACC) of Bartholins gland is a rare gynecologic malignancy. We report two cases from primary treatment to recurrence and the adjuvant treatment. CASE REPORT A woman aged 37 years presented with a mass on the right posterior labia minor and underwent right radical hemi-vulvectomy and right-side inguino-femoral node dissection. Final pathology showed ACC arising from Bartholins gland with positive margins. She received adjuvant external beam radiation to the pelvis, right vulva, and groin area. However, distal metastasis occurred 42 months after initial treatment and she eventually died of multiple metastases. Another woman aged 48 years presented with a mass on the right posterior labia with intermittent pain. She underwent right hemi-vulvectomy and right inguino-femoral lymph node dissection only because pathology showed ACC of Bartholins gland with negative surgical margins. Lung metastasis occurred 59 months after initial treatment. She took tamoxifen only and achieved stable disease status for 4 years. CONCLUSION To date, about 70 cases have been reported. We treated our second patient with antiestrogen therapy for 4 years and achieved good quality of life and stable disease status. However, further study on hormone therapy for ACC of Bartholins gland is needed.

Management of Pelvic Lymphocysts by Ultrasound-Guided Aspiration and Minocycline Sclerotherapy

Objective: The purpose of this study was to describe our experience with ultrasound-guided aspiration of postoperative pelvic lymphocysts followed by intracavitary minocycline injection as sclerotherapy. Patients and Methods: From 1997 to 2003, patients who developed either symptomatic or persistent lymphocyst after pelvic lymphadenectomy for gynecological malignancy were recruited in this study. All of the lymphocysts were palpable and were further examined by ultrasonography. Percutaneous ultrasound-guided needle aspiration of the lymphocyst was performed and then immediately followed by a single-dose injection of minocycline into the collapsed cavity. Follow-up was conducted every 4 weeks with pelvic examination and ultrasonography. Results: Nineteen patients with a total of 21 pelvic lymphocysts underwent this procedure. The median size of the lymphocysts was 6 cm in diameter (range, 4–9 cm). Fifteen patients received 1 treatment, 3 received 2, and 1 patient with bilateral lymphocysts received 3 treatments. Complete resolution occurred in 14 patients (74%), and the other 5 patients (26%) had partial resolution with the volume of the lymphocyst decreasing at least 50%. For the 14 patients with complete resolution, the median time from treatment to disappearance of the lymphocyst was 3 months (range, 1–10 months), and none of them developed recurrence during the average follow-up period of 40 months (range, 2–62 months). No significant complication occurred with this procedure except for transient mild to moderate pelvic pain. Discussion: Minocycline sclerotherapy seems to be a simple and safe method with a satisfactory success rate in treating lymphocysts which develop after pelvic lymphadenectomy. It can be performed in an outpatient setting and can be repeated if necessary. This procedure may be considered as the initial treatment modality for patients suffering from symptomatic or persistent lymphocysts after radical gynecological surgery.

Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Papanicolaou smears

OBJECTIVE To study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears. MATERIALS AND METHODS The medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests. RESULTS The incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14-3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38-0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25-0.44, p<0.0001, respectively). CONCLUSIONS Pregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components.

Stage III malignant mixed Müllerian tumor of the fallopian tube: a case of 5-year survival after optimal debulking and adjuvant chemotherapy with paclitaxel plus carboplatin.

Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan c Institute of Biomedical Nutrition, Hung Kuang University, Taichung, Taiwan d Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan

Metastatic fallopian tube carcinoma presenting as an inguinal hernia.

a Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan b Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan c College of Medicine and Nursing, Hungkuang University, Taichung, Taiwan d Department of Obstetrics and Gynecology, Chung Shan Medical University, Taichung, Taiwan e Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan f Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan