Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; vaginal versus other sites.

Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.

BACKGROUND: MicroRNA (miRNA) expression is known to be deregulated in cervical carcinomas. However, no data is available about the miRNA expression pattern for the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or their combinations to understand their tumorigenesis pathway and to identify diagnostic or prognostic biomarkers. We also investigated the association between those miRNAs and their target genes, especially Notch1 and Notch2. METHODS: We evaluated miRNA expression profiles via miRNA microarray and validated them using.real-time PCR assays with 24 formalin-fixed, paraffin-embedded tissue blocks of MDA and 11 normal proliferative endocervical tissues as control. Expression for Notch1 and 2 was assessed by immunohistochemistry. RESULTS: MiRNA-135a-3p, 192-5p, 194-5p, and 494 were up-regulated, whereas miR-34b-5p, 204-5p, 299-5p, 424-5p, and 136-3p were down-regulated in MDA compared with normal proliferative endocervical tissues (all P<0.05). Considering the second-order Akaike Information Criterion consisting of likelihood ratio and number of parameters, miR-34b-5p showed the best discrimination power among the nine candidate miRNAs. A combined panel of miR-34b-5p and 194-5p was the best fit model to discriminate between MDA and control, revealing 100% sensitivity and specificity. Notch1 and Notch2, respective target genes of miR-34b-5p and miR-204-5p, were more frequently expressed in MDA than in control (63% vs. 18%; 52% vs. 18%, respectively, P<0.05). MiR-34b-5p expression level was higher in Notch1-negative samples compared with Notch1-positive ones (P<0.05). Down-regulated miR-494 was associated with poor patient survival (P=0.036). CONCLUSIONS: MDA showed distinctive expression profiles of miRNAs, Notch1, and Notch2 from normal proliferative endocervical tissues. In particular, miR-34b-5p and 194-5p might be used as diagnostic biomarkers and miR-494 as a prognostic predictor for MDA. The miR-34b-5p/Notch1 pathway as well as Notch2 might be important oncogenic contributors to MDA.

Clear cell carcinomas of the ovary: a multi-institutional study of 129 cases in Korea with prognostic significance of Emi1 and Galectin-3.

Accurate diagnosis of ovarian clear cell carcinoma (CCC) is important because of its poor prognosis with chemoresistance and a high recurrent rate. The clinicopathologic characteristics and prognostic significance of the cell cycle regulator [early mitotic inhibitor-1 (Emi1)] and galactoside-binding protein (Galectin-3) were evaluated. Among 155 CCCs from 18 hospitals in Korea between 1995 and 2006, 129 pure CCCs were selected with consensus using immunohistochemical stains for hepatocyte nuclear factor-1ß, Wilms' tumor protein, and estrogen receptor. The expressions of Emi1, Galectin-3, p53, and Ki-67 labeling index were analyzed with clinicopathologic parameters and the patient's survival. The mean age of the patients was 49.6 yr; the tumors were bilateral in 10.9%, and the average size was 12 cm. Adenofibromatous component was found in 7%, and endometriosis in 48.1% of the cases. Psammoma body was seen in 16.3%. Disease-free survival and overall survival rates were 78.3% and 79.1%, respectively. The International Federation of Obstetrics and Gynecology (FIGO) stage was the most important prognostic indicator. Emi1 expression (>5%) was seen in 23.3% of CCCs, and associated with high FIGO grades and poor overall survival (P<0.05). High Galectin-3 (≥80%) expression was seen in 59.7% of CCCs, and associated with FIGO stages III and IV, and high Ki-67 labeling index. High Ki-67 labeling index (≥50%) and p53 expression (≥50%) were seen in 27.1% and 18.6% of CCCs, respectively, but there was no clinicopathologic and prognostic significance. On the basis of the fact that the expression of Emi1 in CCC was correlated with a high histologic grade and worse overall survival, target therapy using inhibitors of Emi1 may be tried in the management of CCC patients with Emi1 expression.

Adenoma malignum of the uterine cervix: imaging features with clinicopathologic correlation.

BACKGROUND: Adenoma malignum, also known as minimal deviation adenocarcinoma, is a subtype of mucinous adenocarcinoma of the cervix. PURPOSE: To evaluate the clinical, pathologic, and imaging features of the adenoma malignum of the uterine cervix. MATERIAL AND METHODS: We retrospectively analyzed the CT and MRI findings in 13 patients: size, endoluminal fluid, appearance of the solid and cystic component, margin, enhancement, characteristics of locules of the cystic lesion, tumor spread, and associated ovarian lesion. Clinical and pathologic features were determined in 24 patients. RESULTS: The mean of the major tumor diameter was 4.1 cm (range, 2.2-6.5 cm). In the imaging features, 77% of 13 tumors demonstrated endoluminal fluid. All tumors showed enhancing solid components; 62% were multicystic and 38% had solid lesions. Most solid lesions exhibited an irregular margin (80%). The locules of the multicystic lesions tended to have smooth margins (75%), to have an average major diameter of ≤1 cm (88%), and to be 11-20 in number (75%). The solid lesions were associated with invasion and metastases (60%). Clinically, 38% of 24 patients had watery discharge and 13% had Peutz-Jeghers syndrome, while pathologically, most patients were low stage (I or II) (83%). Over the 2-year follow-up of 17 patients, 82% was free from disease. The patients with more aggressive tumors or an unfavorable prognosis that manifested as tumor recurrence or metastasis tended to have invasion, watery discharges, high stages (III or IV) (100%) and solid lesions, metastases, and associated ovarian lesions (67%). CONCLUSION: Awareness of imaging features as well as clinicopathologic manifestations of adenoma malignum can aid in accurate diagnosis, treatment, and prediction of prognosis.

Rate of vertical transmission of human papillomavirus from mothers to infants: relationship between infection rate and mode of delivery.

BACKGROUND: In contrast to consistent epidemiologic evidence of the role of sexual transmission of human papillomavirus (HPV) in adults, various routes may be related to HPV infection in infants. We have assessed the extent of HPV infection during the perinatal period, and the relationship between mode of delivery and vertical transmission. RESULTS: A total of 291 pregnant women over 36 weeks of gestation were enrolled with informed consent. Exfoliative cells were collected from maternal cervix and neonatal buccal mucosa. HPV infection and genotypes were determined with an HPV DNA chip, which can recognise 24 types. The HPV-positive neonates were re-evaluated 6 months after birth to identify the presence of persistent infection. HPV DNA was detected in 18.9 % (55/291) of pregnant women and 3.4 % (10/291) of neonates. Maternal infection was associated with abnormal cytology (p = 0.007) and primiparity (p = 0.015). The infected neonates were all born to HPV-positive mothers. The rate of vertical transmission was estimated at 18.2 % (10/55) which was positively correlated with maternal multiple HPV infection (p = 0.003) and vaginal delivery (p = 0.050), but not with labour duration and premature rupture of membranes. The rate of concordance of genotype was 100 % in mother-neonate pairs with vertical transmission. The neonatal HPV DNAs found at birth were all cleared at 6 months after delivery. CONCLUSIONS: Vertical transmission of HPV DNA from HPV infected mother to the neonate increased when the infant was delivered through an infected cervix. However, the absence of persistent infection in infants at 6 months after delivery may suggest temporary inoculation rather than true vertical infection.

Treatment with medroxyprogesterone acetate plus levonorgestrel-releasing intrauterine system for early-stage endometrial cancer in young women: single-arm, prospective multicenter study: Korean gynecologic oncology group study (KGOG2009).

A prospective multicenter trial has been started in Korea to investigate the treatment efficacy of a levonorgestrel-releasing intrauterine system plus medroxyprogesterone acetate in young women with early-stage endometrial cancer. A number of studies have reported the effectiveness of hormonal therapy using systemic progestin in women clinically diagnosed with early endometrial adenocarcinoma at Stage IA, Grade 1, who want to maintain reproductive potential. In addition, several recent studies reported the use of a levonorgestrel-releasing intrauterine system to treat patients at a high risk of perioperative complications who cannot tolerate systemic progesterone because of its adverse effects. However, there has been no prospective multicenter trial that investigated the effectiveness of treatment with systemic progesterone in combination with intrauterine progesterone in young women with endometrial cancer. Young patients with histologically confirmed Grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium, who desired to preserve their fertility potential, undergo levonorgestrel-releasing intrauterine system insertion and are administered medroxyprogesterone acetate at a dosage of 500 mg/day concurrently. The follow-up and treatment response assessment were implemented at a 3-month interval with office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in place, and dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system. The primary endpoint is the complete response rate. The secondary endpoint is to estimate the consistency of the results of the office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in the uterus and a dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system.

Metastatic urachal carcinoma of the ovary.

A 52-year-old woman had undergone a partial cystectomy for a cystic mass at the dome of the urinary bladder in 1997. The pathological diagnosis was a urachal mucinous cystadenoma with borderline malignancy. Twelve years later, multiple masses were noted on the uterus, ovaries and abdominal wall. She underwent debulking surgery, including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, infracolic omentectomy, appendectomy, colon mass removal and abdominal wall mass removal. Remnants of the tumor were seeded throughout the abdominal cavity. The pathological evaluation confirmed metastatic urachal mucinous adenocarcinoma in both ovaries, the abdominal wall, the colon mass, the uterosacral ligament and the bladder. Adjuvant chemotherapy with paclitaxel and carboplatin was administered, which showed stable disease. She is now undergoing second-line chemotherapy.

Association between atypical endometriosis and ovarian malignancies in the real world.

BACKGROUND: To evaluate the clinical outcome of atypical endometriosis and its association with ovarian malignancy. METHODS: This retrospective study included patients diagnosed with atypical endometriosis between January 2001 and December 2017. All patients had received surgical treatment for ovarian tumor. The clinical characteristics and histopathological results of all patients were reviewed. RESULTS: Atypical endometriosis was diagnosed in 101 patients. We analyzed 98 patients with a mean age of 34.8 years (range: 16-58 years). Ten patients (10.2%) had previously undergone endometriosis surgery more than once. In total, 12 (12.2%) patients had atypical endometriosis-associated ovarian malignancy-nine had carcinomas and three had borderline tumor. The tumors were pathologically classified as follows: five, clear cell carcinomas; two, endometrioid adenocarcinomas; one, mixed clear cell and endometrioid adenocarcinoma; one, seromucinous carcinoma; two, mucinous borderline tumors; and one, seromucinous borderline tumor. CONCLUSION: Atypical endometriosis is most frequently associated with clear cell carcinoma and endometrioid adenocarcinoma. To identify the risk of ovarian malignancy and manage patients with endometriosis, diagnosing atypical endometriosis and recognizing its precancerous potential are important.

Laparoscopy-assisted vaginal versus abdominal hysterectomy in endometrial cancer.

INTRODUCTION: The purpose of this study was to compare the efficacy of a laparoscopy-assisted surgical staging with a traditional laparotomy staging for the treatment of endometrial cancer. METHODS: We retrospectively analyzed the medical records of 465 patients with endometrial adenocarcinoma treated by surgery between January 1996 and December 2007. RESULTS: There were no significant differences between the laparoscopy and the laparotomy groups in age, body mass index, and histologic type. However, in the laparotomy group, grade and surgical stage were higher, the diseases were more chronic, and more postoperative adjuvant treatments were necessary. One hundred seven (76.4%) of 140 patients in the laparoscopy group and 260 (80.0%) of the 325 patients in the laparotomy group had lymphadenectomy, and the median numbers of pelvic and paraaortic lymph nodes obtained were not statistically different. The laparoscopy group showed shorter postoperative hospital stay and lower blood loss, and the operating time was also shorter than that in the laparotomy group. There was no significant difference in intraoperative or postoperative complications, and the operative technique did not influence survival rates after adjusting several confounding factors. CONCLUSIONS: Our data of 12 years with a large number of patients show no differences in complications and impacts on survival between laparoscopy and laparotomy. Laparoscopy has advantages of shorter operating time and other advantages over laparotomy previously reported. Therefore, laparoscopy can be considered a good therapeutic option for endometrial cancer.

Absence of the septum pellucidum associated with a midline fornical nodule and ventriculomegaly: a report of two cases.

We report two autopsy cases that revealed the partial absence of the septum pellucidum with ventriculomegaly. In each case, the brain showed mild dilatation of both frontal horns of the lateral ventricles, normal third and fourth ventricles and no aqueductal stenosis. The posterior portion of the septum pellucidum was absent and the fornices were fused in a single midline nodule, abnormally displaced to a caudal position and lodged in the foramina of Monro. The brain base showed no apparent abnormalities; the optic nerves were well developed. We conclude that the caudally displaced fornix in the absence of the septum pellucidum may have intermittently obstructed the foramina of Monro and induced mild ventriculomegaly.

A Phase II, Prospective, Randomized, Multicenter, Open-Label Study of GX-188E, an HPV DNA Vaccine, in Patients with Cervical Intraepithelial Neoplasia 3.

PURPOSE: To determine the efficacy of the therapeutic DNA vaccine GX-188E for inducing regression of cervical intraepithelial neoplasia (CIN) 3. PATIENTS AND METHODS: We conducted a prospective, randomized, multicenter, open-label, phase II clinical trial of GX-188E in CIN3 patients positive for human papillomavirus (HPV) type 16/18. The primary endpoint was to determine the histopathologic regression to ≤CIN1 at visit seven (V7; 20 weeks after the first GX-188E injection), and an extension study was pursued until visit 8 (V8; 36 weeks after the first GX-188E injection). HPV-sequencing analysis and an ex vivo IFNγ ELISpot assay were performed using the collected cervical biopsy and blood samples from patients. RESULTS: In total, 72 patients were enrolled and underwent randomization. Of them, 64 patients were included in per-protocol analysis (V7) and 52 in extension analysis (V8). Our data showed 52% (33/64) of patients at V7 and 67% (35/52) of patients at V8 presented histopathologic regression after receiving the GX-188E injection. We found that 73% (V7) and 77% (V8) of the patients with histologic regression showed HPV clearance. HPV clearance and histopathologic regression were significantly associated at V7 and at V8. Compared with the measurements at V1 (baseline), the patients at V8 with HPV clearance showed significantly higher fold changes in their IFNγ ELISpot responses compared with those without HPV clearance. The HPV sequence analysis revealed that the HPV type 16 E6/E7 variants D25E, V83L, and N29S were inversely associated with histopathologic regression at V8. CONCLUSIONS: GX-188E is an effective therapeutic vaccine against a cohort containing only CIN3 patients.

Changes of vaginal microbiota during cervical carcinogenesis in women with human papillomavirus infection.

OBJECTIVE: To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection. MATERIALS AND METHODS: Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer. RESULTS: A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms increased in patients with CIN or cervical cancer with HPV infection. Atopobium vaginae (OR 4.33, 95% CI 1.15-16.32), Dialister invisus (OR 4.89, 95% CI 1.20-19.94), Finegoldia magna (OR 6.00, 95% CI 1.08-33.27), Gardnerella vaginalis (OR 7.43, 95% CI 1.78-31.04), Prevotella buccalis (OR 11.00, 95% CI 2.00-60.57), and Prevotella timonensis (OR 6.00, 95% CI 1.46-24.69) were significantly associated with the risk of CIN 2/3 or cervical cancer. CONCLUSION: Women with the CIN and cervical cancer showed a high diversity in vaginal microbiota. Depletion of Lactobacillus crispatus and increased abundance of anaerobic bacteria were detected in women with cervical disease.

Status of HPV vaccination among HPV-infected women aged 20-60 years with abnormal cervical cytology in South Korea: a multicenter, retrospective study.

OBJECTIVES: Since 2007, human papillomavirus (HPV) vaccines have been administered for the prevention of cervical cancer in Korea. We investigated the status of HPV vaccination among HPV-infected adult women with abnormal cervical cytology before the introduction of National Immunization Program. METHODS: From 2010 to 2016, HPV-positive women (age, 20-60 years) with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, and clinical data, including HPV vaccination history, were obtained. We compared the epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated and unvaccinated women. RESULTS: Among the 1,300 women, approximately 26% had a history of vaccination. Vaccinated patients were significantly younger, unmarried, and had a higher education level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was a significant younger age at vaccination initiation (p=0.025), longer duration from HPV vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women (adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29-0.88). For women with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% CI=0.13-0.96). CONCLUSION: This study highlighted the status of HPV vaccination and the prevalence of HPV-16/18 genotypes among HPV-infected women with abnormal cervical cytology according to HPV vaccination. It provides preliminary information regarding the status of HPV vaccination among Korean adult women.

Conservative treatment with progestin and pregnancy outcomes in endometrial cancer.

INTRODUCTION: The purpose of this study was to evaluate the efficacy of conservative treatment with progestin and pregnancy outcomes in women with early-stage endometrial cancer. METHODS: We retrospectively analyzed the medical records of 35 patients with endometrial adenocarcinoma, who were treated with progestin from January 1996 to December 2006. Women with early-stage grade 1 endometrioid endometrial adenocarcinoma, who wanted to receive conservative treatment or preserve fertility, were included. All women were treated with medroxyprogesterone acetate or megestrol acetate, with regular dilation and curettage performed. Complete remission (CR) was defined as no evidence of endometrial adenocarcinoma or hyperplasia. Partial remission was diagnosed when the patient developed endometrial hyperplasia, and persistent disease was defined as residual endometrial adenocarcinoma by pathologic confirmation. RESULTS: The median age was 31 years (range, 21-43 years), and the median follow-up period was 39 months (range, 5-108 months). Complete remission was achieved in 22 patients (62.9%), partial remission was achieved in 1 patient (2.9%), and 12 patients (34.3%) had persistent disease. The median time to CR was 9 months (range, 2-12 months). Of the 22 patients with CR, 9 (40.9%) had recurrent disease, and the median time to recurrence was 12 months (range, 8-48 months). Ten (83.3%) of the 12 patients with CR who tried to conceive were successful, and 8 of the 10 pregnancies resulted in live births. There were no congenital anomalies in babies associated with progestin treatment. CONCLUSIONS: Conservative treatment with progestin can be considered a good therapeutic option in patients with well-differentiated early-stage endometrioid endometrial adenocarcinoma who wish to preserve their uteri or become pregnant.

Human papillomavirus genotype-specific risk in cervical carcinogenesis.

OBJECTIVE: To evaluate the risk of genotype-specific human papillomavirus (HPV) infections for the spectrum of cervical carcinogenesis and the distribution of HPV types according to age and different cervical lesions. METHODS: This study included HPV-positive women who underwent cervical biopsy at the Cheil General Hospital & Women's Healthcare Center between July 1, 2011 and December 31, 2017. HPV genotyping was conducted using a Cheil HPV DNA chip kit. RESULTS: The study sample consisted of 400 normal, 399 cervical intraepithelial neoplasia (CIN) 1, 400 CIN 2, 400 CIN 3, and 389 cervical cancer cases. HPV 16 was the most common type found with a prevalence of 9.5% in normal, 6.8% in CIN 1, 15.0% in CIN 2, 44.5% in CIN 3, and 64.3% in cervical cancer. The most common HPV types were 16, 52, 58, 53, 51, 56, 68, and 18 in all study samples. HPV 16, 31, 33, and 58 were more common in CIN 2/3 and cancer, and HPV 39, 51, 53, 56, 66, and 68 were more common in CIN 1 and normal cases (p<0.001). In CIN 3 and cervical cancer, HPV 16 was the most common type in all age groups. HPV 52 was the most common type in CIN 2 (all age groups) and in CIN 1/normal (age ≤30 years) cases. Among the high-risk HPV types, 16, 31, 33, 52, and 58 showed significant risk for high-grade disease. CONCLUSIONS: HPV 16, 31, 33, 52, and 58 showed the significant risk of high-grade disease for cervical carcinogenesis.

Yolk sac tumor of the ovary: CT findings.

BACKGROUND: The purpose of this study was to evaluate computed tomographic (CT) findings of pathologically proven yolk sac tumors of the ovary. METHODS: Two radiologists retrospectively evaluated CT findings of 10 yolk sac tumors in consensus. The presence of bright dot sign; laterality; presence of necrosis; size, margin, and shape of the mass were analyzed. RESULTS: Mean age of patients was 22 years (ranging from 11 to 34 years). Mean size of the tumors was 14 cm (ranging from 11.1 to 18.5 cm). All 10 tumors showed bright dot sign, necrotic portion, and smooth margin in post-contrast CT scan. All the tumors were unilateral. Nine of 10 tumors showed oval shape. CONCLUSIONS: On CT scans, ovarian yolk sac tumors appeared as large, unilateral, smooth marginated mass with bright dot sign and necrotic portion.

Risk factors for cytological progression in HPV 16 infected women with ASC-US or LSIL: The Korean HPV cohort.

OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20-60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08-2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P<0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01-17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.

Immunohistochemical study of DNA topoisomerase I, p53, and Ki-67 in uterine carcinosarcomas.

Uterine carcinosarcomas (UCs) are highly aggressive neoplasms for which no effective adjuvant therapy has been established. The aim of this study was to test potential indicators of UC sensitivity to topoisomerase I (topo I)-targeted drugs. Laboratory studies have shown that the cellular response to topo I-targeted drugs is dependent on topo I expression, DNA replication rate, and activity of the apoptotic pathway. Therefore, this study investigated expression of topo I, a proliferation marker Ki-67, and the apoptosis initiator p53 in 20 cases of UC. Formalin-fixed paraffin-embedded tissue sections were immunostained with monoclonal antibodies against topo I, Ki-67, and p53. The hospital records of all 20 patients with UC were reviewed. Twelve (60%) of 20 cases showed increased expression of topo I. Staining for Ki-67 showed elevated expression in 15 (75%) of 20 cases. Fourteen cases (70%) showed positive staining for p53 in more than 20% of the tumor cells. However, analysis of the relationship between immunohistochemical results and clinical parameters revealed no correlations with topo I expression. There were no significant correlations between the expression of topo I and Ki-67 (P = .704), or topo I and p53 (P = .465). Significantly increased expression of topo I, Ki-67, and p53 in UC tumor cells suggests sensitivity to topo I-targeted drug treatment.

Comparison of two preparation methods for endocervical evaluation.

OBJECTIVE: To assess the validity of SurePath liquid-based preparation method for examination of endocervical brush specimens as a substitute for conventionally prepared cytology methods for evaluating the endocervical canal during colposcopic examination and biopsy. STUDY DESIGN: Paired SurePath liquid-based test slides and conventional smears were obtained using an endocervical brush in a split sample protocol before biopsy at the time of colposcopy. The level of agreement between cytologic results obtained was assessed. Accuracy and operating characteristics were evaluated compared to histologic follow-up. RESULTS: Agreement between cytology results for the methods was excellent. The overall kappa was 0.924 (p = 0.0000). There was exact agreement on interpretation between the methods in 283 of 299 cases (94.6%). Cytohistologic follow-up results correlation were: SurePath liquid-based Pap test results and conventional smear results agreed with histology results in 47.8% and 49.2% of cases, respectively. Allowing for a discrepancy within 1 level of severity of cytologic grade, agreements were 76.6% and 77.2%, respectively. CONCLUSION: This study demonstrates that the SurePath method is equivalent to conventional endocervical brush cytology preparation and performs well for detection of cervical intraepithelial lesions and cancer. SurePath is acceptable for endocervical evaluation as a substitute for endocervical curettage at colposcopic biopsy.

Clinicopathological significance of atypical glandular cells on cervicovaginal Pap smears.

OBJECTIVE: To evaluate the histologic correlation and clinical significance of atypical glandular cells (AGC) detected on Pap tests. METHODS: Pap tests interpreted as AGC were retrieved from an institutional cytopathology database. The AGC subcategories according to the Bethesda system 2001 include atypical glandular cells, not otherwise specified (AGC-NOS), atypical endometrial cells (AEM), and atypical endocervical cells (AEC). Clinicopathologic variables were collected from medical records retrospectively, and histologic follow-up diagnoses were correlated with AGC subcategories. RESULTS: From January 2009 to December 2014, 741 (0.17%) of 435 778 cervical smears were interpreted as AGC. Of 713 cases included in the study analysis, the distribution of AGC subcategories was as follows: AGC 15.3%, AEM 59.6%, and AEC 25.1%. Of 508 cases with histologic follow-up results, 33.9% of cases were diagnosed to have clinically significant lesions, which include cervical squamous or glandular neoplasia (1.4% and 10.0%), endometrial neoplasia (21.5%), and other metastatic carcinoma (1.0%). Endometrial neoplasia was the most common significant pathology in women aged ≥40 years (28.4%), whereas cervical glandular neoplasia was the most commonly diagnosed lesion in women aged <40 years (14.5%, P < 0.001). When considering past histories which could affect the Pap results, IUD use (10.3%) and pregnancy (7.3%) were most frequently documented. Although IUD users showed low prevalence of significant pathology (2.6%), AGC cases related with pregnancy preceded significant pathologic lesions in 14.3%. CONCLUSIONS: The relatively high incidence of significant neoplasia linked to AGC emphasizes the importance of adherence to the AGC management guidelines which recommend early and intensive investigation using multiple testing modalities.