Is Estrogen Receptor Assessment Necessary in Well Differentiated Invasive Ductal Carcinomas (IDCs) Graded by the Nottingham Combined Histologic Scoring System?
Aaron L Klein, Josh A Hanson, Andrew Goodwin, Donald L Weaver, Abiy B Ambaye. Fletcher Allen Health Care, Burlington, VT; University of Vermont, Burlington
Background: Hormone therapy is the standard of care for invasive carcinomas positive for estrogen and progesterone receptors (ER/PR). ASCO/CAP guidelines recommend reporting a positive result if ≥1% of tumor cells stain for ER. In addition, the guidelines warn that up to 20% of ER/PR assays are reported incorrectly, usually due to false negative results. Studies have shown that IDCs with low nuclear grade are ER/PR positive. However, the correlation of ER/PR positivity with IDCs graded according to the Nottingham scoring system is not well established. Our data indicates that well differentiated IDCs are positive for ER in nearly 100% of cases, thereby questioning the application of ER/PR assays in these tumors.
Design: 2,065 cases of IDC from 2000 to 2010 were retrospectively assessed. ER and PR quantification was performed on formalin fixed, paraffin embedded tissue and was interpreted by one of three breast pathologists. The association between Nottingham tumor grade, nuclear grade, and ER/PR expression was examined.
Results: 595 cases of well differentiated IDC were included, of which eight (1.3%) were negative for ER (<1% nuclear staining) (table). Two tumors were mucinous, one had apocrine features, one was papillary, one was intracystic, and one tumor had DCIS with microinvasion. The eight ER negative tumors were PR negative in all but one case. Moderately and poorly differentiated IDCs were negative for ER in 8.2% and 51.1% respectively. ER negativity with respect to nuclear grade was observed in 0.9%, 3.4%, and 43.1% of nuclear grade I, II, and III IDCs, respectively.
|Differentiation||Total #||ER neg (p<0.0001)||PR neg (p<0.0001)|
|well||595||8 (1.3%, 95% CI 0.6%-2.6%)||45 (7.6%, 95% CI 5.6%-10.0%)|
|mod||834||68 (8.2%)||139 (16.7%)|
|poor||636||325 (51.1%)||344 (54.0%)|
|Nuclear Grade||Total #||ER neg (p<0.0001)||PR neg (p<0.0001)|
|I||112||1 (0.9%, 95% CI 0.02%-4.9%)||11 (9.8%, 95% CI 5.0%-16.9%)|
|II||1122||38 (3.4%)||43 (3.8%)|
|III||831||358 (43.1%)||405 (48.7%)|