Accounts for approximately 10% of all ovarian serous carcinomas.
Low-grade serous carcinoma (LGSC) of the ovary, fallopian tube, or peritoneum accounts for approximately 5% of epithelial ovarian cancer, and is clinically, histologically, and molecularly different from the more common and high grade serous lesion.
Distinct from other ovarian cancers by unique histologic, molecular and clinical manifestations.
Has a more indolent course and a more favorable prognosis compared to high-grade serous carcinomas of the ovary.
More resistant to chemotherapy than high-grade serous carcinomas of the ovary.
Median onset of age at diagnosis is 43 years.
It has a bimodal age distribution.
Older patients with presentation more commonly display, mitogen activated protein kinase (MAPK) , and have a better overall prognosis, wheras younger patients have a poorer prognosis.
LGSC patients are often diagnosed at advanced stage, with approximately 60% of patients presenting stage III and higher.
Tumors are categorized with a low mitoticindex, most have positive immunohistochemistry for PAX8 and WT1 and a small minority a Tp53.
Lesions display hormone receptor positivity in 50 to 90% of cases with estrogen receptor positivity and 40-60 % with positive progesterone receptor activity.
High grade serous carcinoma, is thought to originate in the fallopian tube, LGSC typically arises denovo or in a sequential fashion progressing from a benign ovarian tumor to a serous borderline tumor and ultimately LGSC.
Studies report a 4 to 7% risk of malignant progression among all patients with serous borderline tumors.
In a recurrent setting response rate to chemotherapy less than 4%.
KRAS mutations 20-40%, and BRAF mutations 5-33%.
Associated with increased frequency of expression of activated protein kinase (MAPK).
Expression of MAPK in low-grade serous ovarian cancers is 81% compared to 41% in high-grade lesions.
Fewer than 5% of patients with low-grade serouscarcinoma carry germline BRCA1 or BRCA2 alterations.
Treatment:
Surgery is the mainstay of treatment.
There is an association of residual disease after cytoreductive surgery with poor patient outcomes.
Primary cytoreductive surgery with maximal surgical effort should be undertaken and followed by platinum based chemotherapy or hormonal treatments for patients with higher stage disease.
There is evidence that hormonal blockade following surgery/chemotherapy with letrozole maintenance is associated with a greater median progressive free survival.
For patients with recurrent disease a secondary cytoreduction is recommended.
For patients with who are not candidates for surgery, options include chemotherapy, hormonal blockade, or MEK inhibition
Selumetinib an oral potent, selective, small molecule inhibitor of MAPKMEH1/2 promising agent.