The amount of preoperative endometrial tissue surface in relation to final endometrial cancer classification.

OBJECTIVE: To evaluate whether the amount of preoperative endometrial tissue surface is related to the degree of concordance with final low- and high-grade endometrial cancer (EC). In addition, to determine whether discordance is influenced by sampling method and impacts outcome. METHODS: A retrospective cohort study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC). Surface of preoperative endometrial tissue samples was digitally calculated using ImageJ. Tumor samples were classified into low-grade (grade 1-2 endometrioid EC (EEC)) and high-grade (grade 3 EEC + non-endometroid EC). RESULTS: The study cohort included 573 tumor samples. Overall concordance between pre- and postoperative diagnosis was 60.0%, and 88.8% when classified into low- and high-grade EC. Upgrading (preoperative low-grade, postoperative high-grade EC) was found in 7.8% and downgrading (preoperative high-grade, postoperative low-grade EC) in 26.7%. The median endometrial tissue surface was significantly lower in concordant diagnoses when compared to discordant diagnoses, respectively 18.7 mm2 and 23.5 mm2 (P = 0.022). Sampling method did not influence the concordance in tumor classification. Patients with preoperative high-grade and postoperative low-grade showed significant lower DSS compared to patients with concordant low-grade EC (P = 0.039). CONCLUSION: The amount of preoperative endometrial tissue surface was inversely related to the degree of concordance with final tumor low- and high-grade. Obtaining higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade diagnosis in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome.

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer.

OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.

Prognostic impact of CD133 expression in Endometrial Cancer Patients.

To assess the impact of CD133 expression on the prognosis of endometrioid endometrial carcinoma (EEC). We retrospectively assessed CD133 expression in tissue microarray of 116 surgically treated FIGO I-III EEC. Tumors with ≥10% of CD133-expressing cells were considered CD133-positive (CD133+). On the basis of CD133 expression, clinical and pathological parameters, progression-free survival (PFS) and overall survival (OS) were evaluated. Of the EEC studied 85.2% showed CD133-expressing cells. Only 61% (n = 66) of EEC presented ≥10% of CD133 expressing cells and were considered CD133+. The mean OS for CD133+ tumour patients was 161 months (95% CI, 154-168) as compared with 146 months (95% CI, 123-160) for those with CD133- tumors (p = 0.012). The mean PFS for CD133+ tumour was 159 months (95% CI, 149-168) as compared with 147 months (95% CI, 132-161) in those with a CD133-tumour (p = 0.014). CD133+ tumours were less likely to have vascular invasion (p = 0.010) and more likely to be well differentiated (p = 0.034). C133+ tumours predicted favorable OS and PFS of EEC patients, with a Hazard Ratio 4.731 (95% CI, 1.251-17.89; p = 0.022). CD133+ tumor status correlates with favorable prognosis of EEC. Our findings are in agreement with studies addressing brain and colorectal tumours.

Urine human papillomavirus prevalence in women with high-grade cervical lesions.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) in urine samples from women with high-grade cervical lesions. Secondary objectives are to identify the influence of socio-demographic factors and the different genotypes with urinary HPV positivity. STUDY DESIGN: 75 women with a positive biopsy for CIN2+ were included in the study from October 2010 to July 2011. A sample of urine was collected immediately before conization at the outpatient clinic. We analyzed the presence of HPV using a PCR technique. RESULTS: The mean age of the patients was 34.8 years (range 24 to 61). All patients had histological CIN2+, of whom 54.67% had CIN3. The prevalence of HPV in urine test was 58.82% in CIN2 population versus 78.05% in CIN3 patients (p 0.072). 31 different genotypes were found. The most frequent HPV genotype was 16-HPV, which was identified in 58% of women with positive HPV-DNA in urine samples. No demographic characteristics were significantly associated to urinary HPV prevalence. CONCLUSION: Most of the patients with CIN2+ showed positive results for urine HPV test. The prevalence of positive urinary HPV test was higher for patients with CIN3. HPV urine detection could be considered as an acceptable option for high-risk population who skip regular screening programs.

Out-of-protocol concurrent use of cisplatin and radiation therapy in locally advanced cervical cancer: feasibility and survival.

PURPOSE OF INVESTIGATION: We assessed the feasibility, response rates, and overall survival of patients with locally advanced cervical cancer treated with cisplatin-based chemotherapy during radiation therapy on an out-of-protocol basis. METHODS: Sixty-nine consecutive newly diagnosed untreated patients with locally advanced cervical cancer who received chemoradiation between 1999 and 2003 were retrospectively reviewed. Treatment consisted in external beam radiation followed by one 137-cessium intracavitary application. Cisplatin was administered for six weeks during external beam radiation. RESULTS: Treatment was well tolerated, although 52 patients presented some degree of acute adverse toxicity (gastrointestinal 65%, hematological 48%, genitourinary 10%). The 3-year survival rate was 61.8% (95% CI 54.5-69.0), with a mean 41.8 months (95% CI 35.7-48.3). Overall survival after adjusting by FIGO Stage IB2-IIA and IIB-IVA was 73.9% and 50%, respectively (p = 0.1839). Overall survival according to Stages IB2-IIb and III-IVA was 74.8% and 34.9%, respectively (P = 0.0376). CONCLUSION: In patients with locally advanced cervical cancer, adding a weekly regimen of cisplatin to standard pelvic radiation in an out-of-protocol basis is feasible, effective, and showed no unexpected toxicity.

A study of Ki-67, c-erbB2 and cyclin D-1 expression in CIN-I, CIN-III and squamous cell carcinoma of the cervix.

The histological criteria for cervical intraepithelial neoplastic lesions and their follow-ups have been established, but their reproducibility, specificity and sensibility are not certain. Immunohistochemical markers provide more information on each specific case, in order to facilitate its classification and, eventually, its prognosis. Using immunohistochemical techniques, this study analyzes the prognostic value of three markers (Ki-67, c-erbB2 and Cyclin D1) in cases of low grade squamous intraepithelial neoplasia (CIN-I), high grade squamous intraepithelial neoplasia (CIN-III), and infiltrating squamous cell carcinoma (SCC) taken from a group of cervical samples. In situ hybridization was performed in order to detect high-risk HPV. High risk HPV was demonstrated in 82%, 89% and 100% of the LGSIL, HGSIL and SCC cases, respectively. C-erbB2 expression was detected in 9%, 33% and 50% of the LSIL, HGSIL and SCC cases, respectively. The Ki-67 LI was 25%, 68% and 65.5% in the LGSIL, HGSIL and SCC cases, respectively. Nuclear Cyclin D1 expression was seen in 82%, 11% and 30% of the CIN-I,CIN-III and SCC cases, respectively. We observed that the cytoplasmic cyclin D1 expression increased with the severity of the lesion instead of the nuclear expression decreasing with the progression of the pathology. Nuclear and cytoplasmic Cyclin D1 expression seemed to be related to HPV high risk infection. We concluded that Cyclin D1, cerbB2 and The Ki-67 LI expression changed in relation to the severity of the lesion and that they could be helpful in making a differential diagnosis.

The Ki-67 labeling index is not a useful predictor for the follow-up of cervical intraepithelial neoplasia 1.

OBJECTIVE: Our aim was to determine whether the Ki-67 immunostaining pattern, present on diagnosis of cervical intraepithelial neoplasia (CIN), predicts the change from low-grade to high-grade CIN over a 2-year period after diagnosis. MATERIALS AND METHODS: Of 59 cervical biopsy samples from 59 patients diagnosed as having cervical CIN, 35 were diagnosed as CIN 1 and 24 were diagnosed as CIN 2 or CIN 3. The Ki-67 immunostain showed immunopositive cells in the upper two thirds of the epithelium in all specimens. Two hundred nuclei were counted in 25 high-power fields in each specimen, including all of the epithelial layers, to determine the mean number of Ki-67-positive cells. In situ hybridization was used to demonstrate and type human papillomavirus. The chi test, Fisher exact test, Student t test, one-way analysis of variance, and Tukey test were used for statistical analysis, with significance set at p < .05. RESULTS: The mean Ki-67 labeling index for CIN 1, CIN 2, CIN 3, and CIN 2,3 were, respectively, 32.5%, 43.2%, 53.2%, and 47.8%. The statistical study showed significant differences between CIN 1 versus CIN 2, CIN 1 versus CIN 3, and CIN 1 versus CIN 2,3. For CIN 1, the mean Ki-67 labeling index was 32.8% when the lesion disappeared and was 34.6% for persisting lesions. There was no statistically significant difference. CONCLUSIONS: Ki-67 labeling index did not predict persisting CIN 1.

Atipia citológica de significado incierto en células escamosas. Importancia del seguimiento de las pacientes. Relación con la edad y las células metaplásicas / Atypical squamous cells of undetermined significance. Importance of patient follow-up and relation with age and metaplastic cells

Objetivos: Evaluar la importancia de la edad y de las células sobre las que asientan las lesiones de atipia citológica de significado incierto en células escamosas (ASCUS) en relación con la evolución de la lesión. Material y método: Revisión de las citologías correspondientes a 296 pacientes diagnosticadas de ASCUS (ASC-US y ASC-H), desde 1995 a 1999 en el Servicio de Patología del Hospital del Mar de Barcelona. Evaluación de la aparición de displasia de cualquier grado en uno de los controles posteriores, en relación con los antecedentes, con el tipo de células sobre las que asientan los cambios, y con la edad de las pacientes. Resultados: Antecedentes: La tasa de aparición de lesión escamosa intraepitelial de bajo grado (LSIL) es variable y no tiene relación con los antecedentes de la paciente. La tasa de aparición de lesión escamosa intraepitelial de alto grado (HSIL) muestra un aumento lineal en relación con la gravedad de los antecedentes. Edad: Se observa mayor tasa de aparición de LSIL en mujeres menores de 45 años y mayor tasa de aparición de HSIL en mujeres mayores de 45 años, pero las diferencias no son estadísticamente significativas. Células escamosas inmaduras: Se observa mayor tasa de aparición de lesión escamosa intraepitelial (SIL) de cualquier grado cuando los cambios asientan sobre células escamosas inmaduras, pero las diferencias no son estadísticamente significativas. Conclusiones: Sí parecen tener importancia los antecedentes en relación con la recidiva de la lesión. Pese a que la tasa de aparición de HSIL es baja, aumenta en relación con la gravedad de los antecedentes. La identificación de una citología ASCUS en una paciente con antecedentes de displasia puede marcar la progresión-evolución del proceso displásico. Parece, además, que HSIL es más frecuente cuando ASCUS asienta sobre células escamosas inmaduras. Nuestros datos favorecen esta hipótesis, a pesar de que las diferencias no son estadísticamente significativas. Respecto a la edad, nuestro estudio confirma los datos establecidos previamente en la bibliografía. Por fin, parece importante el hecho de realizar controles citológicos al menos durante los primeros 2 años, dado que la tasa de aparición de HSIL es mayor en este período (AU)

Nuevas perspectivas en el tratamiento quirúrgico del carcinoma de cérvix. Papel de la laparoscopia / New options in the surgical treatment of cervical cancer. Place of the laparoscopy

Se revisa el papel de la laparoscopia en estadios iniciales y avanzados y en las recidivas del cáncer de cuello uterino. Se comenta el empleo de la técnica en situaciones especiales como, combinada con la vía vaginal, en pacientes jóvenes (traquelectomía). (AU)