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TRANSCRIPT
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OVARY CANCER. I.
(Prof. A. Riccardi)
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EPIDEMIOLOGY
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OVARIAN CANCER (OC)
Epidemiology. I.* leading cause of death from gynecologic
cancers;
- in USA, 23,100 new cases diagnosed (in
2000) and 14,000 deaths;
- 5% of all cancer deaths in women (% > thoseof cervical and endometrial cancer
combined);
* incidence > with age and peaks in the 8th
decade (uncommon < age of 40, unlike germ
cell and stromal tumors)
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GYNECOLOGICAL CANCERS: INCIDENCE AND DEATHS
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STAGING AND SURVIVAL IN GYNECOLOGIC MALIGNANCIES
Stage OVARIAN 5-yrsurvival %
ENDOMETRIAL 5-yrsurvival %
CERVIX 5-Yearsurvival, %
0 - - carcinoma in situ 100I confined
to ovary90 confined to corpus 89 confined to uterus 85
II confinedto pelvis
70 involvescorpus and cervix
80 invades beyonduterus but not to
pelvic wall
60
III intraabdominalspread
15-20 extends outside theuterus but not outside
the true pelvis
30 extends to pelvicwall and/or
lower third ofvagina, or
hydronephrosis
33
IV spread outsideabdomen 1-5 extends outside truepelvis or involvesbladder or rectum
9 invades mucosaof bladder orrectum or
extends beyondthe true pelvis
7
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* survival: excellent with early stage (rare)but poor when extensive disease (most
frequent at diagnosis);
- improved survival and cure rate in
advanced OC from aggressive multimodal
therapy with surgery radiation chemotherapy
OVARIAN CANCER (OC)
Epidemiology. II.
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OVARIAN CANCER
Epidemiology. II.* higher incidence in industrialized countries;
* < risk with each pregnancy (by 10%), breast
feeding, tubal ligation, oral contraceptives;
* > risk with disordered ovarian function (infertility,
nulliparity, frequent miscarriages, use of ovulation-inducing drugs such as clomiphene)
= "incessant ovulation" hypothesis for OC etiology
i.e., an aberrant repair process of the surfaceepithelium is central to OC development;
* estrogen replacement after menopause for < 11
yrs does not increase the risk
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* depending on histologic cell type:- ovarian germ cell tumors: young non
white women;
- epithelial tumors: postmenopausal white
women
OVARIAN CANCEREpidemiology. II.
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ETIOLOGY AND GENETICS
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* about 5% of all OC, with a family history being
major risk factor (life-time risk = 1.6, 5.0 and 50% in thegeneral population, in women with one, and > one
affected first-degree relative, respectively);
* 3 types of autosomal dominant familial OC:- site-specific (only OC);
- cancer of ovary and breast;
- Lynch type II cancer family syndrome (non-polyposis colorectal cancer, endometrial cancer, and
OC)
OVARIAN CANCER
Etiology and genetics. I.Familial cancers. I.
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OVARIAN CANCER
Etiology and genetics. II.Familial cancers. II.* two susceptibility loci in hereditary breast - ovarian
cancer:
- BRCA-1(chr 17,q12-2) and BRCA-2 (chr 13, q12-13);
- both tumor suppressor genes (= the protein product
is a negative regulator of tumor growth);- most mutations (frameshift or nonsense mutations)
produce not pathological, truncated protein products;
* cumulative risk of OC with critical mutations = 25% (50% for breast cancer);
* > risk of prostate cancer in men
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OVARIAN CANCER
Genetics
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OVARIAN CANCERGenetics
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OVARIAN CANCERGenetics
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OVARIAN CANCERGenetics
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BRCA GENE
ASSOCIATED
CANCERS
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SALPINGO-OOPHORECTOMY AND
SURVEILLANCE FOR OVARIAN CANCER.
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* complex karyotypic rearrangements[structural abnormalities on chrs 1 and 11, loss
of heterozygosity (LOH) on 3q, 6q, 11q, 13q,
and 17];
* frequent oncogene abnormalities (including
c-myc, H-ras, K-ras, and neu)
OVARIAN CANCEREtiology and genetics. III.Sporadic cancers
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* usually, within complex genetic syndromes:
- ovarian sex cord stromal tumors in women andSertoli cell tumors in men in Peutz-Jeghers
syndrome (mucocutaneous pigmentation and
intestinal polyps);- gonadoblastomas in gonadal dysgenesis (46 XY
genotype or mosaic for Y-containing cell lines);
- ovarian fibromas in pts with nevoid basal cell
carcinomas
OVARIAN CANCER
Etiology and genetics. IV.Not epithelial OC
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CLINICAL PRESENTATION
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OVARIAN CANCERClinical presentation. I.
* most pts first diagnosed when the disease
has already spread beyond the true pelvis;
- localized OC generally asymptomatic;
- progressive enlargement can produceurinary frequency or constipation (rarely,
torsion of an ovarian mass causes acute
abdominal pain and / or surgical abdomen)
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OVARIAN CANCER
Clinical presentation. II. Early disease* diagnosis from palpation of asymptomatic
adnexal mass during routine pelvic
examination;
- in pre-menopausal women usually benign
functional cysts (typically, resolve over 1 - 3menstrual cycles);
- in peri- or post-menopausal women more
likely malignant (a solid, irregular, fixed pelvic
mass is usually OC)
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* several other causesf adnexal masses:
- redundant colon;
- paraovarian cysts;
- ectopic pregnancy;
- pedunculated uterineibroids
Early ovarian cancer
Differential diagnosis. I.
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Early ovarian cancer
Differential diagnosis. II.
- inflammatory or
neoplastic bowel
lesions;
- policystic kidney;- retroperitoneal
neoplasms;
- tubo-ovarian cysts
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OVARIAN CANCER
Clinical presentation. III. Advanced disease
- present and ignored for long periods (75%
of OC are disseminated at diagnosis):- abdominal pain;
- increased abdominal girth;
- bloating, and
- urinary symptoms;
* rarely, vaginal bleeding or discharge (# to
cervical or endometrial cancer)
OVARIAN CANCER
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OVARIAN CANCER
Serum Ca-125* glycoprotein (MM = 220 - 1000 kDa) useful for
evaluation of pts with suspected OC;
- levels > 35 U / mL in > 80% of pts with epithelial OC;- elevated levels in other cancers (of endometrium,
cervix, fallopian tubes, pancreas, breast, lung, and
colon), in nonmalignant conditions (pregnancy,endometriosis, pelvic inflammatory disease, and
uterine fibroids) and in 1% of normal females;
* OC probable in post-menopausal women with anasymptomatic pelvic mass and CA-125 > 65 U/mL
(sensitivity = 97%, specificity = 78%)
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OVARIAN CANCER
Screening. I.
* pts with early OC (stages I and II) are commonly
curable with conventional therapy = effective
screening procedures are expected to improve the
cure rate;
- pelvic examination: insensitive;- transvaginal sonography: significant false+ results
(particularly in pre-menopausal women), possibly
reduced by associating doppler flow imaging;- CA-125: < 65 U / mL in 50% of stage I and II OC
and > 65 U/mL in nonmalignant disorders (= false- and
false+ results)
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OVARIAN CANCER
Screening. II.Combining transvaginal ultrasound and CA-125
* in a study (22,000 women), only 11 / 42 with+screen had OC and 8 with -screen had OC = high
false+ rate (leading to unnecessary laparotomies);
- NCI Consensus Conference against screening forOC in women without known risk factors;
- annual pelvic examinations, transvaginal
ultrasound, and CA-125 to screen women with afamily history of OC or breast / ovarian cancers?