Serous tumors of low malignant potential of the ovary-molecular pathology: part 2

Abstract

A progressive development from serous tumors of low malignant potential (SLMP) to bluntly invasive serous carcinoma has been suggested in parallel to the concept of adenoma-carcinoma sequence in colorectal carcinomas. However, recent genetic data enforces a reassessment of the concept that SLMP tumors represent precursor lesions to invasive serous carcinoma. Despite the benign nature of the majority of these tumors, some will behave worse. The identification of those SLMP tumors with an aggressive clinical behavior remains difficult, regardless of a growing body of molecular pathologic investigations. Expression of p53, c-erbB2, as well as the presence of ras mutations are not helpful in this respect. Immunostaining of both MMP-2 and basement membrane components such as collagen type IV, as well as the disintegration of collagen type I at the tumor-host interface, may be helpful for the diagnosis of a microinvasive SLMP, but it remains questionable whether this is important for prognosis. The differential diagnosis to frankly invasive carcinoma depends on the detection of destructive stromal invasion. In questionable cases, the loss of N-cadherin would argue for the presence of a carcinoma whereas the coexpression of p21 and MDM2 is rather characteristic for SLMP tumors.

Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

“…low-grade serous carcinomas, along with low-grade endometrioid, mucinous and clear cell tumors, are thought to develop step-wise from benign cystadenomas/adenofibromas via borderline tumors and are typically slowly proliferating and frequently harbor mutations in KRAS, BRAF and PTEN . In contrast, type 2 tumors (high-grade serous and high-grade endometrioid ovarian tumors, carcinosarcomas and undifferentiated carcinomas) are suggested to develop from precursor lesions in the fallopian tube [24] and are characterized by rapid progression and frequent TP53 mutations [10], [34]–[36]. Molecular subtyping of ovarian cancer is being increasingly recognized, with e.g.…”

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“…Borderline tumours of the ovary display many but not all characteristics of malignancy including nuclear atypia and increased mitotic count, usually in the absence of stromal invasion [21-24]. Whether the borderline tumour is a precursor to the fully malignant ovarian carcinoma or a disease distinct from invasive carcinomas is a topic that has been debated since the International Federation of Gynaecologic Oncology added the borderline tumour to the classification of ovarian tumours in 1972.…”

In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low‐grade serous tumours

“…Ovarian serous neoplasms exhibit a range of morphological appearances, namely adenomas, conventional high‐grade carcinomas, and intermediate forms termed serous borderline tumours (SBTs) 9. Current evidence, based on clinical 10 and genetic data 11 (for review see ref 12), argues for the most part against SBTs being precursors of high‐grade serous carcinomas (SCAs). However, there is evidence that the genetic background of SBT and SCA is similar.…”