Endometrial Intraepithelial Neoplasia - Biology

Biology

EIN lesions demonstrate all of the behaviors and characteristics of a premalignant, or precancerous, lesion.

Precancer Features of EIN (Table I). The cells of an EIN lesion are genetically different than normal and malignant tissues, and have a distinctive appearance under the light microscope. EIN cells are already neoplastic, demonstrating a monoclonal growth pattern and clonally distributed mutations. Progression of EIN to carcinoma, effectively a conversion from a benign neoplasm to a malignant neoplasm, is accomplished through acquisition of additional mutations and accompanied by a change in behavior characterized by the ability to invade local tissues and metastasize to regional and distant sites.

Table I: Precancer Characteristics of EIN

Precancer Characteristics EIN Evidence
Precancers differ from normal tissue
  • Monoclonal EIN arise from polyclonal normal field.
  • Mutations are acquired in EIN.
Precancers share some, but not all, features of cancer
  • EIN-cancer lineage hierarchy
  • EIN may share PTEN, K-ras, MLH1 changes with cancer.
  • Both EIN and cancer are monoclonal.
Precancers increase risk for carcinoma
  • Elevated concurrent cancer rate (39% in first year after EIN diagnosis)
  • EIN elevates future cancer risk 45-fold.
Precancers can be diagnosed
  • Morphometric reference standard (D-Score) for EIN diagnosis.
  • Subjective EIN diagnosis using criteria (Table 2).
Cancer must arise from cells within the precancer
  • EIN-cancer lineage hierarchy.
  • EIN may share PTEN, K-ras, MLH1 changes with resultant cancer.

EIN Biomarkers. (Figure 1). There are no single biomarkers which are completely informative in recognition of EIN. The tumour suppressor gene PTEN is frequently inactivated in EIN, being abnormally turned off in approximately 2/3 of all EIN lesions. This can be seen with special tissue stains applied to histological sections known as PTEN immunohistochemistry, in which the brown PTEN protein is seen to be absent in the crowded tubular glands that make up an EIN lesion.

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