Franco Odicino

Carcinoma of the ovary

Ovarian cancer is staged surgically. There should be histologic confirmation of the disease. Operative findings, prior to tumor debulking, determine stage, which may be modified by histopathologic as well as clinical or radiological evaluation. Laparotomy and resection of the ovarian mass, as well as hysterectomy, form the basis for staging. Biopsies of all suspicious sites, such as omentum, mesentery, liver, diaphragm, pelvic and paraaortic nodes, are required. The final histologic findings after surgery (and cytologic ones when available) are to be considered in the staging. Clinical studies include routine radiology of the chest. Imaging studies and serum tumor markers may be helpful in both initial staging and follow-up of the tumors.

Carcinoma of the corpus uteri

Notes about the staging Histopathology – degree of differentiation: Cases of carcinoma of the corpus should be grouped with regard to the degree of differentiation of the adenocarcinoma as follows: • G1: 5% of a nonsquamous or nonmorular solid growth pattern • G2: 6−50% of a nonsquamous or nonmorular solid growth pattern • G3: >50% of a nonsquamous or nonmorular solid growth pattern Notes on pathologic grading: • Notable nuclear atypia, inappropriate for the architectural grade, raises the grade of a Grade 1 or Grade 2 tumor by 1. • In serous and clear cell adenocarcinomas, nuclear grading takes precedent. • Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component. Rules related to staging: • Corpus cancer is now surgically staged, therefore procedures previously used for determination of stages are no longer applicable (e.g. the findings of fractional curettage to differentiate between Stage I and Stage II). • It is appreciated that there may be a small number of patients with corpus cancer who will be treated primarily with radiation therapy. In these cases, the clinical staging adopted by FIGO in 1971 would still apply, but designation of that staging system would be noted. • Ideally, width of the myometrium should be measured along with the depth of tumor invasion.

Carcinoma of the cervix uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer.

Primary site The cervix is the lower third of the uterus. It is roughly cylindrical in shape, projects through the upper, anterior vaginal wall and communicates with the vagina through an orifice called the external os. Cancer of the cervix may originate on the vaginal surface or in the canal. Nodal stations The cervix is drained by preureteral, postureteral, and uterosacral routes into the following first station nodes: parametrial, internal (obturator – hypogastric), external iliac, presacral and common iliac. Para-aortic nodes are second station and are considered metastases.

History of the FIGO cancer staging system

The main objectives of any good staging system – essential to an evidence‐based approach to cancer – are: to aid the clinician in planning treatment; to provide indication of prognosis; to assist the physician in evaluating the results of treatment; to facilitate the exchange of information between treatment centers, thus disseminating knowledge; and to contribute to continuing investigations into human malignancies. A good staging system must have 3 basic characteristics: it must be valid, reliable, and practical. The first staging system for gynecological cancers appeared around the turn of the 20th century and applied to the carcinoma of the cervix uteri—the most common cancer affecting women in high income countries at that time. The classification and staging of the other gynecological malignancies was not put forward until the 1950s. Over the years, these staging classifications – with the exception of cervical cancer and gestational trophoblastic neoplasia – have shifted from a clinical to a surgical–pathological basis. This paper reviews the history of the International Federation of Gynecology and Obstetrics (FIGO) cancer staging system, how it was developed, and why.

Cancer in women.

Incidence, mortality and survival trends for the most frequent cancers affecting women are presented on a worldwide basis. Data sources are represented by several different cancer databases, as no single world cancer database covers these epidemiological measures. Monitoring cancer incidence, mortality and survival are fundamental indicators which allow estimates and predictions of geographical and temporal changes of these diseases, enabling the design and set‐up of adequate cancer control activities and national health programs. The observed differences in cancer incidence, mortality and survival in more developed countries compared with less developed countries (as defined by WHO) are mainly due to different individual and social risk factors between the two geo‐political areas. For some cancers, advancements in screening, diagnosis and treatment in the more developed areas were the most effective factors in reducing incidence and mortality as well as prolonging survival. These effects were not detected in the less developed areas because of the limited access to primary and specialist care.

Carcinoma of the vulva. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer.

Primary site Cases should be classified as carcinoma of the vulva when the primary site of growth is in the vulva. Tumors present in the vulva as secondary growths, from either a genital or extra-genital site, have to be excluded. Malignant melanoma should be separately reported. A carcinoma of the vulva that extends into the vagina should be considered as a carcinoma of the vulva. There must be histologic confirmation of the cancer.

Carcinoma of the vulva

Primary site Cases should be classified as carcinoma of the vulva when the primary site of growth is in the vulva. Tumors present in the vulva as secondary growths, from either a genital or extra-genital site, have to be excluded. Malignant melanoma should be separately reported. A carcinoma of the vulva that extends into the vagina should be considered as a carcinoma of the vulva. There must be histologic confirmation of the cancer.

Gestational Trophoblastic Neoplasia

The pathologic classification and histologic findings of gestational trophoblastic neoplasia are discussed.

Serum Human Epididymis Protein 4 and Risk for Ovarian Malignancy Algorithm as New Diagnostic and Prognostic Tools for Epithelial Ovarian Cancer Management

Background: The aim of this work was to analyze the diagnostic and prognostic value of serum human epididymis protein 4 (HE4) and Risk for Ovarian Malignancy Algorithm (ROMA) in epithelial ovarian cancer (EOC). Methods: Preoperative serum samples of 419 women (140 healthy controls, 131 ovarian benign cysts, 34 endometriosis, and 114 EOC) were tested for CA125 and HE4 using fully automated methods (Abbott ARCHITECT) and validated cutoff values. Results: For the discrimination of benign masses from EOC, in premenopausal women, the sensitivity and specificity were 92.3% and 59.4% for CA125, 84.6% and 94.2% for HE4, and 84.6% and 81.2% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 94.3% and 82.3% for CA125, 78.2% and 99.0% for HE4, and 93.1% and 84.4% for ROMA. In patients with EOC, elevated CA125, HE4, and ROMA levels were associated with advanced Federation of Gynaecologists and Obstetricians (FIGO) stage, suboptimally debulking, ascites, positive cytology, lymph node involvement, and advanced age (all P ≤ 0.05). Elevated HE4 and ROMA (both P ≤ 0.01), but not CA125 (P = 0.0579), were associated with undifferentiated tumors. In multivariable analysis, elevated HE4 and ROMA (all P ≤ 0.05) were independent prognostic factors for shorter overall, disease-free, and progression-free survival. Conclusions and Impact: This study underlines the high specificity of HE4 in discriminating endometriosis and ovarian benign cysts from EOC and the high sensitivity of CA125 in detecting EOC. We showed HE4 and ROMA as independent prognostic factors. Multicenter studies are needed to draw firm conclusions about the applicability of HE4 and ROMA in clinical practice. Cancer Epidemiol Biomarkers Prev; 20(12); 2496–506. ©2011 AACR.

Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients

Background:To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis.Methods:Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4–EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated.Results:Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort.Conclusion:We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.