Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma.

The coexistence of endometriosis (ES) with ovarian clear cell carcinoma (CCC) or endometrioid carcinoma (EC) suggested that malignant transformation of ES leads to endometriosis associated ovarian carcinoma (EAOC). However, there is still lack of an integrating data analysis of the accumulated experimental data to provide the evidence supporting the hypothesis of EAOC transformation. Herein we used a function-based analytic model with the publicly available microarray datasets to investigate the expression profiling between ES, CCC, and EC. We analyzed the functional regularity pattern of the three type of samples and hierarchically clustered the gene sets to identify key mechanisms regulating the malignant transformation of EAOC. We identified a list of 18 genes (NLRP3, AIM2, PYCARD, NAIP, Caspase-4, Caspase-7, Caspase-8, TLR1, TLR7, TOLLIP, NFKBIA, TNF, TNFAIP3, INFGR2, P2RX7, IL-1B, IL1RL1, IL-18) closely related to inflammasome complex, indicating an important role of inflammation/immunity in EAOC transformation. We next explore the association between these target genes and patient survival using Gene Expression Omnibus (GEO), and found significant correlation between the expression levels of the target genes and the progression-free survival. Interestingly, high expression levels of AIM2 and NLRP3, initiating proteins of inflammasomes, were significantly correlated with poor progression-free survival. Immunohistochemistry staining confirmed a correlation between high AIM2 and high Ki-67 in clinical EAOC samples, supporting its role in disease progression. Collectively, we established a bioinformatic platform of gene-set integrative molecular functionome to dissect the pathogenic pathways of EAOC, and demonstrated a key role of dysregulated inflammasome in modulating the malignant transformation of EAOC.

Robotic-assisted laparoscopic complex myomectomy: a single medical center's experience.

OBJECTIVE: Conventional laparoscopic myomectomy (LM) has inherent limitations due to its rigid structure. The robotic system is a newly developed technology equipped with a flexible EndoWrist that offers good performance in delicate motions. Our objective was to share our clinical experience in the management of complex myomectomy using this robotic system. MATERIALS AND METHODS: From October 2010 to March 2012, 21 patients with symptomatic complex uterine myomas were evaluated. Complex myomectomy was defined as surgery involving more than two fibroids, large fibroids, or preexisting pelvic adhesions. We recorded and analyzed the preoperative characteristics of the patients and the fibroids, the detailed surgical time, and several postoperative outcomes to evaluate the feasibility and efficacy of robotic-assisted LM (RALM) for complex fibroids. RESULTS: A total of 21 patients were enrolled in this study. The mean age of the patients was 40.1 ± 4.5 years and the mean size of the largest fibroid was 7.3 ± 3.5 cm. RALM achieved satisfactory results, including a short postoperative hospital stay (3.1 ± 0.9 days), a low conversion rate (none of our patients required conversion to either a minilaparotomy or conventional open surgery), and a low complication rate (1 case in 21 patients, 4.8%). The average estimated blood loss was 235.7 ± 283.3 mL. CONCLUSION: Our study results demonstrated that RALM is a safe and effective method for handling complex fibroids.

Comparison of early-stage primary serous fallopian tube carcinomas and equivalent stage serous epithelial ovarian carcinomas.

OBJECTIVE: To investigate the outcome of patients with early-stage primary fallopian tube carcinomas (PFTC) and those of patients with equivalent-stage serous epithelial ovarian carcinomas (SEOC). MATERIALS AND METHODS: A balanced and matched, case-control comparison was conducted in a university-based tertiary hospital database between 1978 and 2007. All PFTC and SEOC patients were treated with complete staging surgery followed by multiagent chemotherapy. One SEOC control was matched for each PFTC patient in a very uniform manner (characteristics and treatment). Disease-free survival (DFS) and overall survival (OS) were then compared using Kaplan-Meier analysis. RESULTS: Twenty-six paired patients were analyzed. Patients with PFTC were significantly older than the SEOC patients (58 years vs. 51 years, p = 0.001). In terms of recurrence, PFTC patients frequently had an extra-abdominal metastasis (3/4, 75%), in contrast to the SEOC patients, who did not (1/5, 20%). The 5-year DFS rate was similar in both groups (85% vs. 81%, p = 0.05), contributing to a similar OS rate (89% vs. 85%, p = 0.50). The median DFS and OS of patients with PFTC and SEOC were also similar without a statistically significant difference (125 months vs. 109 months, and 125 months vs. 122 months, respectively). CONCLUSION: Our study demonstrated that the survival outcome of International Federation of Gynecology and Obstetrics (FIGO) I/II PFTC patients was similar to that of FIGO I/II SEOC patients, and both groups had a >80% 5-year DFS rate after complete staging surgery, followed by multiagent chemotherapy. This finding is worthy of being investigated.

Outcome of patients with bulky IB (≥ 6 cm) cervical squamous cell carcinoma with and without cisplatin-based neoadjuvant chemotherapy.

OBJECTIVE: To study the surgical morbidity and outcomes of patients with markedly bulky cervical squamous cell carcinoma (≥ 6 cm Cx-SCC) who underwent radical hysterectomy (RH) with and without neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: This retrospective study enrolled patients with International Federation of Gynecology and Obstetrics (FIGO) IB markedly bulky Cx-SCC who were treated with either three courses of weekly single agent cisplatin NACT (50 mg/m2) and subsequent radical hysterectomy (NACT-RH) or direct radical hysterectomy (RH) between 1996 and 2001. A total of 60 patients fulfilled the criteria, including 35 and 25 patients with NsACT-RH and RH, respectively. RESULTS: There was no statistically significant difference in basic characteristics between the two groups, except the smaller pathological tumor size, less blood loss, and lower immediate complication rate in the NACT-RH group. Median survival was 143.8 months in the NACT-RH group and 129.8 months in the RH group, respectively, without a statistically significant difference. Multivariate analysis showed that large pathological tumor size [hazard ratio (HR) 10.66, 95% confidence interval (CI) 2.93-38.80], the presence of para-aortic lymph node metastases and an immediate complication (HR 8.33 and 4.55, 95% CI 1.66-41.75 and 1.35-15.27, respectively) contributed to a worse outcome. CONCLUSION: Weekly single agent cisplatin NACT indeed reduced the pathological tumor size and immediate complication rate during the RH, supporting the feasibility of subsequent RH in the management of patients with bulky Cx-SCC.

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

OBJECTIVE: To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). MATERIALS AND METHODS: This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). RESULTS: Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). CONCLUSION: PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ.

Comparing effectiveness of combined transobturator tension-free vaginal mesh (Perigee) and transobturator tension-free vaginal tape (TVT-O) versus anterior colporrhaphy and TVT-O for associated cystocele and urodynamic stress incontinence.

OBJECTIVE: To evaluate the efficacy and safety of transobturator tension-free vaginal mesh (Perigee) and concomitant transobturator tension-free vaginal tape (TVT-O) for treating cystocele with urodynamic stress incontinence (UDSI). STUDY DESIGN: A retrospective study of 115 patients with symptomatic stages 2-3 cystocele and UDSI who were treated with a Perigee system (Group I, n=68) plus TVT-O procedure or traditional anterior colporrhaphy (Group II, n=47) plus TVT-O procedure. All patients were followed up for more than one year. Objective and subjective symptoms were evaluated at one year postoperatively. Statistical analysis was performed using SPSS software. RESULTS: The objective cure rates for cystocele at one year were significantly higher in Group I than in Group II (98.5% and 86.9%, P=0.018), respectively. The cure rates for UDSI in the two groups were 91.0% vs. 91.3% (P=1.000). Symptomatic improvement of frequency was better in Group I than Group II (87.7% vs. 70.0%, P=0.030). There were no significant differences with regard to intraoperative and postoperative complications between the two groups. CONCLUSIONS: The combination of the Perigee system and TVT-O offers a safe and effective treatment for cystocele with UDSI and may be performed as first-line treatment.

Prognostic nomogram for overall survival in stage IIB-IVA cervical cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVE: On the basis of outcome data from concurrent chemoradiotherapy (CCRT) for locally advanced cervical squamous cell carcinoma, the authors developed a nomogram for predicting survival outcome. STUDY DESIGN: Two hundred fifty-one eligible patients with International Federation of Gynecology and Obstetrics stage IIB-IVA squamous cell carcinoma of the uterine cervix who underwent CCRT were included for the construction of the nomogram. Predictor variables included age, serum squamous cell carcinoma antigen, tumor size, parametrium invasion, hydronephrosis, bladder/rectum invasion, and lymph node metastases. Internal validation of the nomogram was performed. RESULTS: A nomogram for predicting the 5 year overall survival for these patients was constructed on the basis of a Cox regression model from 7 parameters. The concordance index was 0.69. CONCLUSION: This nomogram is a predictive tool, upon external validation, that can be used to counsel patients in predicting outcomes. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death.

Physiology and potential application of NKT cells: a minireview.

CD1d-restricted T (NKT) cells are potent regulators of autoimmunity, tumor immunity, and transplantation-related immunity. NKT cells are a subset of innate lymphocytes that recognize endogenous or exogenous glycolipids in the context of CD1d molecules. Recent progress in the research of NKT cells has proved that NKT cells function as a bridge between innate and adaptive immunity in anticancer immunity. Furthermore, NKT cells also function as a bridge to tolerance or rejection of grafts in organ transplantation. Harnessing the function of NKT cells, and trying to put it into clinical application in the treatment of autoimmune disease, anticancer cell immunotherapy, and organ transplantation are the dreams of immunologists. This minireview will focus on the physiology of NKT cells and potential clinical application.

Aggressive characteristics of cervical cancer in young women in Taiwan.

OBJECTIVE: To compare the characteristics and prognosis of cervical cancer in young women (under 30 years) with those of older women (over 30 years). METHODS: A retrospective study of 2443 patients diagnosed with FIGO stage IA-IIA cervical cancer who underwent surgical procedures between January 1983 and December 2007. RESULTS: Thirty patients (1.2%) were 30 years or younger. The proportion of non-squamous cell carcinoma was higher in patients 30 years or younger compared with in patients over 30 years (14/30, 46.7% vs 10/30, 33.3%; P=0.001). A higher rate of parametrial involvement was found in the younger group of patients compared with those over 30 years (10/30, 33.3% vs 289/2413, 12.0%; P=0.001). Patients under 30 years had a higher rate of distant metastases compared with older patients (60% vs 49.7%; P=0.036). CONCLUSIONS: Non-squamous histology, parametrial involvement, a higher rate of distant metastases, and poorer prognosis are more common in women aged 30 or younger with cervical cancer than in older women with the disease.

Importance of delivered cycles and nomogram for intraperitoneal chemotherapy in ovarian cancer.

OBJECTIVE: Intraperitoneal (IP) chemotherapy has gained enthusiasm in the treatment of ovarian cancer. Despite having a better survival advantage than intravenous (IV) chemotherapy, IP chemotherapy still poses significant morbidity and complications. Identifying the subset of patients who could best benefit from IP chemotherapy, and those who would least benefit from this treatment, thus avoiding potential complications, is critical. METHODS: Between January 2001 and December 2007, 367 patients with stage III epithelial ovarian cancer underwent randomized trial for IP/IV chemotherapy were recruited to construct a nomogram, which is a graphical representation of Cox proportional hazards model adopting six weighted risk factors including age, CA125, IP/IV delivery, stage, histology, and upper abdominal metastases. The nomogram was internally validated for discrimination and calibration. The concordance index was used for quantifying the predictive ability of overall survival with bootstrapping to correct for bias. RESULTS: The cycles of completed IP chemotherapy had an impact on overall survival (> or =5 vs. < or =4 cycles, P=0.02). A nomogram for predicting median survival and 5-year survival probability was constructed with a concordance index of 0.72. Upper abdominal tumor metastases (P<0.001) and colon resection (P=0.02) predicted increased chances for early discontinuation of IP chemotherapy. CONCLUSIONS: At least five IP cycles are needed to achieve better survival. Nomogram can help to identify the subset of patients who can least benefit from IP chemotherapy, thus avoiding potential IP complications and help to facilitate discussion between patient and physician, risk stratification, and help to guide clinical care.

Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery.

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination--conventional intramuscular injection, electroporation-mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery--in the ability to generate antigen-specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin's role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials.

The relationship between human papillomavirus and Epstein-Barr virus infections in relation to age of patients with cervical adenocarcinoma.

OBJECTIVE: To examine the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) infections in relation to age of patients with cervical adenocarcinoma. MATERIALS AND METHODS: Thirty samples of human cervical adenocarcinoma tissue were collected from the surgical pathology archive at Taipei Veterans General Hospital from 1996 to 2008. All samples were examined for EBV, HPV-16 and HPV-18 E6 DNA by conventional and real-time quantitative polymerase chain reaction assays. RESULTS: HPV-16 DNA was detected in 10 cases (33.3%), HPV-18 DNA in 12 cases (40%), and EBV DNA in three cases (10%); there were negative findings in seven cases (23.3%). EBV combined with HPV-16 or HPV-18 was also detected in one case each. No link could be demonstrated between HPV and EBV in endocervical lesions. When 20 patients 45 years old were compared with 10 patients > 45 years old, HPV-18 E6 DNA was detected in 45% vs. 30% (9/20 vs. 3/10), HPV-16 E6 DNA in 40% vs. 20% (8/20 vs. 2/10), EBV DNA in 10% vs. 10% (2/20 vs. 1/10), and no virus DNA was detected in 10% vs. 50% (2/20 vs. 5/10). HPV and EBV were significantly more common in younger women (p < 0.001). CONCLUSION: HPV-18 plays a major role in adenocarcinomas at any age. A high prevalence of HPV DNA is significantly associated with cervical adenocarcinoma, especially in younger women. The results do not support a role for EBV in cervical adenocarcinogenesis or any relationship between EBV and HPV infection in adenocarcinoma.

Regulatory T cells: potential target in anticancer immunotherapy.

The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor alpha-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cell-mediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

Laparoscopic uterosacral nerve ablation with and without presacral neurectomy in the treatment of primary dysmenorrhea: a prospective efficacy analysis.

OBJECTIVE: To evaluate the efficacy of laparoscopic uterosacral nerve (LUNA) alone vs. LUNA plus presacral neurectomy (PN) in the treatment of primary dysmenorrhea. STUDY DESIGN: Seventy-four patients were randomly allocated to LUNA alone or LUNA plus PN. Evaluation of severity of menstrual pain was based on multidimensional scoring. RESULTS: Sixty-seven patients were eligible for analysis (35 LUNA alone, 32 LUNA plus PN). Baseline demographic features were comparable between the 2 groups. There was no difference between them in the proportion of improvement in dysmenorrhea at 3 months of follow-up (69% for LUNA vs. 73% for LUNA plus PN, p = 0.923), and the results were maintained at 6 and 12 months of follow-up. More surgical complications were found in the LUNA plus PN group. CONCLUSION: For patients with primary dysmenorrhea, LUNA plus PN has no additive therapeutic advantage over LUNA alone, and more surgical complications may be encountered.

Efficacy analysis of trans-obturator tension-free vaginal tape (TVT-O) plus modified Ingelman-Sundberg procedure versus TVT-O alone in the treatment of mixed urinary incontinence: a randomized study.

OBJECTIVE: The treatment of women with mixed urinary incontinence still poses a great challenge. This study evaluated surgical outcomes of combined trans-obturator tension-free vaginal tape (TVT-O) and modified Ingelman-Sundberg (IS) procedure for the treatment of mixed urinary incontinence. METHODS: A randomized controlled trial was conducted. Ninety-six women diagnosed with mixed incontinence were randomized, with 49 allocated to TVT-O plus IS and 47 to TVT-O alone. A baseline urodynamic study and evaluation of quality of life (QOL) was conducted. The primary outcome measure was objective assessment of surgical outcomes, and the secondary outcome measure was warning time. RESULTS: Objective surgical response rate was significantly higher in the TVT-O plus IS group than in the TVT-O alone group (84.8% vs. 62.8%; p=0.019). Furthermore, a significant increase in warning time was observed in the TVT-O plus IS group (from 3.9 to 9.4 min; p=0.006), but the increase in warning time within the TVT-O alone group was not statistically significant (from 4.3 to 4.5 min; p=0.695). Postoperative complications were similar in the two study groups with respect to pelvic hematoma, nerve injury, sepsis, mesh erosion, and fistula formation. However, fever occurred more frequently in the TVT-O plus IS group (30.4% vs. 20.9%; p=0.026). CONCLUSIONS: Mixed urinary incontinence can potentially be treated with a one-step combined surgery using trans-obturator sling plus modified IS procedure. Although surgical time and blood loss were significantly increased in the TVT-O plus IS group, overall morbidity was not significantly increased.

Treatment of primary deep dyspareunia with laparoscopic uterosacral nerve ablation procedure: a pilot study.

BACKGROUND: This pilot study was undertaken to evaluate the effect of laparoscopic uterosacral nerve ablation (LUNA) for treatment of primary deep dyspareunia. METHODS: Between July 2002 and June 2003, 12 consecutive patients diagnosed with primary deep dyspareunia were treated with the LUNA procedure. The evaluation scoring system included the Hospital Anxiety and Depression Scale and the revised Sabbatsberg Sexual Rating Scale, done at baseline and 3, 6, and 12 months after LUNA. RESULTS: At the initial 3-month follow-up period, 3 patients were very satisfied with their treatment, 5 were satisfied, 2 uncertain, 1 dissatisfied, and 1 very dissatisfied. The corresponding figures at the 12-month follow-up visit were 2, 4, 4, 1, and 1, respectively. Overall, 8 (66.7%) patients in this trial were very satisfied or satisfied at the initial postoperative evaluation and 6 of them (50.0%) remained satisfied at the final evaluation. CONCLUSION: Over half of the study patients felt satisfied with the results of treatment with LUNA. Further prospective controlled clinical trials are mandatory to validate its effectiveness.

Combined diverticulectomy and anti-incontinence surgery for patients with urethral diverticulum and stress urinary incontinence: is anti-incontinence surgery really necessary?

OBJECTIVE: Urethral diverticulum has been identified in 0.6-6% of women and is diagnosed most frequently in the third to fifth decades. Combined diverticulectomy and anti-incontinence surgery are usually undertaken for patients with urethral diverticulum who present with symptoms of stress urinary incontinence. However, this approach may not always be necessary. CASE REPORT: We report two cases with urethral diverticulum and stress urinary incontinence successfully treated with diverticulectomy only. CONCLUSION: This clinical approach could avoid the potential complications of anti-incontinence surgery.

Successful treatment of deep dyspareunia and primary dysmenorrhea with laparoscopic uterosacral nerve ablation (LUNA) procedure.

Deep dyspareunia, often described as pain resulting from pelvic thrusting during sexual intercourse, is relatively common and has many causes. To date, feasible surgical interventions for deep dyspareunia are very rare. The two procedures which have been mentioned in the literature for the treatment of deep dyspareunia were laparoscopic uterosacral ligament ablation (LUNA) and uterine ventrosuspension. We report the case of a young female patient, aged 32, gravida 3, parity 2, presenting with deep dyspareunia and primary dysmenorrhea for 4 years. She had both subjective and objective improvements for dyspareunia and primary dysmenorrhea following LUNA operation. Further large-scaled randomized controlled trial is mandatory to verify the surgical effect of LUNA operation for patients with deep dyspareunia.

Altered mRNA expressions of sialyltransferases in ovarian cancers.

OBJECTIVE: Aberrant glycosylation occurs in essentially all types of experimental and human cancers, and many glycosyl epitopes constitute tumor-associated antigens (for example, CA125). Many recent studies have indicated that some, if not all, aberrant glycosylation is a result of altered sialyltransferase (ST) expression; however, there is little known of the role of the altered mRNA expression of ST in ovarian cancers. METHODS: Alterations in ST mRNA expression in postmenopausal ovarian tissues, including those of normal controls (n=24) and malignant serous ovarian cancers (n=24), were examined by means of real-time quantitative reverse transcription-polymerase chain reaction (RTQ-PCR). Maackia Amurensis Agglutinin type 2 (MAA) specific foralpha2,3-linked NeuNAc was used for immunohistochemical staining. RESULTS: Among these five STs, the mRNA expressions of three STs, including ST3Gal III, ST3Gal IV, and ST3Gal VI, were significantly decreased in patients with ovarian cancers, compared to the normal controls (P<0.001). By contrast, the mRNA expressions of ST3Gal I and ST6Gal I were increased in ovarian cancer tissues, compared to those of the normal controls (P<0.001). The ovarian epithelial carcinoma part showed strong positivity for MAA, whereas MAA staining in the stromal part was negative. Both the epithelial part and the stromal part of postmenopausal ovarian tissue showed negativity for MAA staining. However, clinico-pathological parameters, including stage, differentiation, amount of ascites, and serum levels of CA125, did not show any correlation to mRNA expression of any given-type ST. CONCLUSIONS: Our results suggest that altered mRNA expressions of alpha2,3-sialyltransferase ST3Gal I, ST3Gal III, ST3Gal IV, ST3Gal VI, andalpha2,6-sialyltransferase ST6Gal I are of importance in malignant ovarian cancers. An increased expression of ST3Gal I may contribute directly to increased alpha2,3-linked sialylation in ovarian serous carcinoma.

Enhanced expression of alpha 2,6-sialyltransferase ST6Gal I in cervical squamous cell carcinoma.

OBJECTIVE: Increased messenger ribonucleic acid (mRNA) expression of beta-galactoside alpha 2,6-sialyltransferase I (ST6Gal I) is important in squamous cell carcinoma (SCC) of the cervix. In many tissues, ST6Gal I is transcriptionally regulated through the use of promoters that originate in the mRNA species that diverge in the 5'-untranslated regions. To clarify the roles of ST6Gal I mRNA species in cervical SCC, we investigated their expression, including a "constitutive" promoter (placental or Y + Z form), "hepatic" promoter (H form), and a specific lymphoblastic promoter (X form), in normal and SCC tissues of the cervix using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR). METHODS: Expression of the ST6Gal I species was investigated in normal cervical tissue samples (n = 38) and FIGO IB1 cervical SCC samples (n = 38) by relatively quantitative real-time RT-PCR, using primers designed for amplification of a portion of the coding region common to all mRNA species or ones for amplification of the placental transcript, the hepatic transcript, or lymphoblastic transcript. RESULTS: ST6Gal I mRNA expression was significantly increased in cancerous tissues compared to that in normal tissues (P = 0.004, Mann-Whitney U test; P < 0.001, paired t test). Expression of the Y + Z form did not appear to be affected by cancer transformation, since it was detected at comparable levels in normal and cancerous tissues (P = 0.986), but H form expression was significantly enhanced in cancerous tissues compared to that in normal tissues (P < 0.001, Mann-Whitney U test and paired t test). Surprisingly, the X form could be detected in some patients with and without cancer, but the detection rate was significantly higher in patients with cancer (86.8% vs 52.6%, respectively; P = 0.021, Fisher's exact test). Although the X transcript was detected at a low level compared to the H and Y + Z transcripts, its expression was also significantly enhanced in patients with cancers compared to those without cancers (P < 0.001, Mann-Whitney U test and paired t test). CONCLUSIONS: An increased level of hepatic transcripts may be important in cancer transformation because the transcripts contribute to enhance ST6Gal I expression in cancerous tissues.