Endometrial Cancer,OB/GYN Hospital Fudan University Xin LU, MD, Ph.D.,Endometriod cancer-Contents,Incidence Risk factors Classification Symptoms,Pathology FIGO Staging Diagnosis Treatment,WHO Cancer Report,Global cancer rates could increase by 50% to 15 million by 2020 Endometrial cancer is the 4th most common cancer in women New Diagnosed cases: 142,000 Died cases each year: 42,000 incidence 2-3% Average age: 60s,Histologic Types,Endometrial Cancers Endometrioid (87%) Adenosquamous (4%) Papillary Serous (3%) Clear Cell (2%) Mucinous (1%) Other (3%),Endometrial Cancer:Type I/II,Type I Estrogen Related Younger and heavier patients Low grade Background of Hyperplasia Perimenopausal Exogenous estrogen Familial/genetic (15% ) Lynch II syndrome/HNPCC Familial trend,Type II (10% ) Aggressive High grade Unfavorable Histology Unrelated to estrogen stimulation Occurs in older & thinner women,Endometrial Cancer: Risk Factors,From: Williams Gynecology 2009,Endometrium Carcinoma 2009 Classification,Stage Characteristic Stage I* Tumor confined to the corpus uteri IA* No or less than half myometrial invasion IB* Invasion equal to or more than half of the myometrium Stage II* Tumor invades cervical stroma, but does not extend beyond the uterus* Stage III* Local and/or regional spread of the tumor IIIA* Tumor invades the serosa of the corpus uteri and/or adnexae# IIIB* Vaginal and/or parametrial involvement# IIIC* Metastases to pelvic and/or para-aortic lymph nodes#. IIIC1* Positive pelvic nodes IIIC2* Positive paraaortic lymphnodes with or without positive pelvic lymph nodes Stage IV* Tumor invades bladder and/or bowel mucosa, and/or distant metastases IVA* Tumor invasion of bladder and/or bowel mucosa IVB* Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes,Endometrial Cancer: FIGO Surgical Stage,Endometrial Cancer Prognosis:,Overall 5Yr Survival 84% Stage and Grade are the most important prognostic factors Altered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept),Aggressive Histologic Subtypes (Clear-cell, Serous) Increasing age (over 65) Vascular invasion Aneuploidy Altered oncogene/tumor suppressor gene expression ( “molecular staging” concept- p53, PTEN, microsatellite instability, MDR-1, HER2/neu, ER/PR, Ki 67, PCNA, CD 31,EGF-R, MMR genes) Race?,Endometrial Cancer: Poor Prognostic Factors,Molecular Genetics,PTEN mutations: 32% Tumor suppressor gene (chrom 10) Phosphatase Early event in carcinogenesis Associated with: endometrioid histology early stage favorable survival,Molecular Genetics,p53 tumor suppressor gene Cell cycle and apoptosis regulation Most commonly mutated gene in human cancers Overexpression (marker for mutation) Associated with poor prognosis early stage: 10% have p53 mutation advanced stage: 50% have p53 mutation not found in hyperplasias late event in carcinogenesis,Genetic Syndromes: HNPCC Hereditary Non-Polyposis Colon Cancer,Lynch II Syndrome Autosomal dominant inheritance MMR (mismatch repair) mutations Genetic instability leads to error-prone DNA replication hMSH2 (chrom 2) hMLH1 (chrom 3) Early age of colon Ca: mean 45.2 years Endometrial Ca: second most common malignancy 20% cumulative incidence by age 70 Earlier age of onset than sporadic cases Other: ovary (3.5-8 fold), stomach, small bowel, pancreas, biliary tract,Diagnosis of disease: Patient Awareness*,More than 95% of patients with Endometrial Cancer report having symptoms Postmenapausal bleeding Menorrhagia Metrorrhagia Bloody Discharge Endometrial biopsy is the main diagnostic tool performed either in the office or via D&C in OR,Uterine Cancer: Diagnosis/Screening,Patient Symptoms/Awareness* Cytology Not a satisfactory screening test Sonography Not Cost effective Hysteroscopy Not Cost effective Histology Secondary to symptoms (not as a screening test),Endometrial Cancer: Transvaginal Ultrasound Screening,Endometrial Cancer: Transvaginal Ultrasound Screening,Endometrial Cancer: Transvaginal Ultrasound Screening,Normal endometrial stripe: Postmenopausal 4- 8 mm Postmenopausal on HRT 4- 10 mm U/S for Detection of any uterine pathology Sensitivity: 85-95% Specificity: 60-80% PPV 2-10% NPV 99%,Summary: Endometrial Cancer: Transvaginal Ultrasound Screening,Hysteroscopy Not satisfactory for screening test,Studies of the efficacy of hysteroscopy as a diagnostic tool vary widely Sensitivity reported ranging from 60-95% compared to D&C obtained at the same time Specificity 50-99%,Hysteroscopy and Positive Cytology?,Studies have been mixed: Some studies suggest an increase in positive peritoneal cytology seen at staging laparotomy in patients who have had hysteroscopy Other studies have failed to find a difference in positive cytology in patients diagnosed via hysteroscopy as compared to office biopsy or D&C,Hysteroscopy Not s