Ovarian Cancer

Ovarian Cancer


        Of all gynecologic malignancies, ovarian cancer continues to have the

highest mortality and is the most difficult to diagnose.  In the United States

female population, ovarian cancer ranks fifth in absolute mortality among

cancer related deaths (13,000/yr).  In most reported cases, ovarian cancer,

when first diagnosed is in stages III or IV in about 60 to 70% of patients

which further complicates treatment of the disease (Barber, 3).


        Early detection in ovarian cancer is hampered by the lack of appropriate

tumor markers and clinically, most patients fail to develop significant symptoms

until they reach advanced stage disease.  The characteristics of ovarian cancer

have been studied in primary tumors and in established ovarian tumor cell lines

which provide a reproducible source of tumor material. Among the major

clinical problems of ovarian cancer, malignant progression, rapid emergence of

drug resistance, and associated cross-resistance remain unresolved.  Ovarian

cancer has a high frequency of metastasis yet generally remains localized

within the peritoneal cavity.  Tumor development has been associated with

aberrant, dysfunctional expression and/or mutation of various genes.  This can

include oncogene overexpression, amplification or mutation, aberrant tumor

suppressor expression or mutation.  Also, subversion of host antitumor immune

responses may play a role in the pathogenesis of cancer (Sharp, 77).


        Ovarian clear cell adenocarcinoma was first described by Peham in 1899

as "hypernephroma of the ovary" because of its resemblance to renal cell

carcinoma. By 1939, Schiller noted a histologic similarity to mesonephric

tubules and classified these tumors as "mesonephromas."   In 1944, Saphir and

Lackner described two cases of "hypernephroid carcinoma of the ovary" and

proposed "clear cell" adenocarcinoma as an alternative term.  Clear cell tumors

of the ovary are now generally considered to be of mullerian and in the genital

tract of mullerian origin. A number of examples of clear cell adenocarcinoma

have been reported to arise from the epithelium of an endometriotic cyst

(Yoonessi, 289).  Occasionally, a renal cell carcinoma metastasizes to the

ovary and may be confused with a primary clear cell adenocarcinoma.


        Ovarian clear cell adenocarcinoma (OCCA) has been recognized as a

distinct histologic entity in the World Health Organization (WHO) classification

of ovarian tumors since 1973 and is the most lethal ovarian neoplasm  with an

overall five year survival of only 34% (Kennedy, 342).  Clear cell

adenocarcinoma, like most ovarian cancers, originates from the ovarian

epithelium which is a single layer of cells found on the surface of the ovary.

Patients with ovarian clear cell adenocarcinoma are typically above the age of

30 with a median of 54 which is similar to that of ovarian epithelial cancer in

general.  OCCA represents approximately 6% of ovarian cancers and bilateral

ovarian involvement occurs in less that 50% of patients even in advanced cases.


        The association of OCCA and endometriosis is well documented (De La

Cuesta, 243).  This was confirmed by Kennedy et al who encountered histologic or

intraoperative evidence of endometriosis in 45% of their study patients.

Transformation from endometriosis to clear cell adenocarcinoma has been

previously demonstrated in sporadic cases but was not observed by Kennedy et al.

Hypercalcemia occurs in a significant percentage of patients with OCCA.

Patients with advanced disease are more typically affected than patients with

nonmetastatic disease.  Patients with OCCA are also more likely to have Stage I

disease than are patients with ovarian epithelial cancer in general (Kennedy,

348).


        Histologic grade has been useful as an initial prognostic determinant in

some studies of epithelial cancers of the ovary.  The grading of ovarian clear

cell adenocarcinoma has been problematic and is complicated by the multiplicity

of histologic patterns found in the same tumor.  Sim
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