BRST2, ER, e-Cadherin, CDX2, and NKX3.1 Utility in Distinguishing Diffuse Gastric from Lobular Carcinoma
Gloria H Lewis, Robert West, Reetesh K Pai, Teri A Longacre, Kristin C Jensen. Stanford University, Stanford, CA; University of Pittsburgh, Pittsburgh, PA; VA Palo Alto HCS, Palo Alto, CA
Background: Distinguishing diffuse gastric (DGC) from lobular breast carcinoma in metastases is morphologically challenging. Few reports on the utility of immunohistochemistry (IHC) are published. We studied a series of gastric (GC) and breast carcinomas (BC) by IHC, including NKX3.1, a prostate marker reportedly expressed in ductal (9%) and lobular (27%) carcinomas.
Design: BRST2, ER, e-cadherin (ECD), CDX2, and NKX3.1 IHC performed on tissue microarrays containing 103 GC and 260 BC were divided based on infiltration pattern: diffuse (single file) vs clustered (tubules/clusters). Mixed cases were considered diffuse. Any IHC labeling was considered positive and correlated by subtype: GC vs BC and diffuse GC (DGC) vs diffuse BC (DBC). P-values were calculated by 2-tailed Fisher's exact test.
Results: IHC are summarized in table 1; sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of DGC vs DBC are in table 2. There were 37 DGC and 99 DBC. ER positivity was seen in tumor cells of 3 GC all of which were DGC (8.6%); however, ER positivity was present in stromal cells in 44.6% (45/101) of GC with negative tumor. Other than GC, the 3 patients with ER positive tumors (2 females and 1 male) had no cancer history. Two cases of BC infiltrating in tubules/clusters (BCTC) negative for NKX3.1, BRST2, and ER were positive for CDX2. The 2 patients had no cancer history other than BC. NKX3.1 was present in comparable proportion of DBC (9.8%) vs BCTC (9.6%) (p=1.0) and in ECD positive (9.9%) vs ECD negative (5.9%) cases (p=0.7).
|BRST2||0 (0/103)||74 (168/227)||0.0001||0 (0/37)||81.5 (66/81)||0.0001|
|ER||2.3 (3/101)||75.9 (173/228)||0.0001||8.6 (3/37)||89.9 (89/99)||0.0001|
|ECD||96.1 (99/103)||83.4 (176/211)||0.0009||91.9 (34/37)||67.5 (52/77)||0.0049|
|CDX2||87.2 (89/102)||0.9 (2/221)||0.0001||91.9 (34/37)||0 (0/79)||0.0001|
|NKX3.1||0 (0/103)||9.2 (21/228)||0.0004||0 (0/37)||9.8 (8/82)||0.0564|