Molecular Pathology Laboratory Network

F HER2 GA

Gastric and gastroesophageal junction (GEJC)cancer

Fluorescence in situ Hybridization (FISH)

3 days

Fix specimen in 10% neutral buffered formalin for at least 6 hours and no longer than 48 hours.

Paraffin block stable at 18-25°C indefinitely

Ship ambient. In summer, ship with a cool/refrigerated pack. (Do not allow cool/refrigerated pack to directly contact sample.)

Improper specimen labeling; Insufficient sample; Inadequate fixation and/or processing

A positive FISH result (HER2/CEP17 ratio greater or equal to 2.0) or an IHC score of 3+ provides eligibility for Herceptin. Patients with IHC scores of 0/1 should not be treated with Herceptin. IHC score of 2+ should be retested using FISH. Any equivocal cases should be retested by an alternate method.

The FDA recently approved trastuzumab (Herceptin, Genentech) for use in combination with cisplatin and capecitabine or 5-fluorouracil to treat patients with human epidermal growth factor receptor 2 (HER2)-over expressing (also called HER2-positive) metastatic gastric or GEJC who have not received prior treatment for metastatic disease. The new indication was largely based upon the results of the “Trastuzumab for Gastric Cancer” or ToGA trial (Lancet. August 28, 2010). The trial revealed that patients on trastuzumab plus chemotherapy had a median overall survival of 13.8 months compared to 11.1 months with chemotherapy alone. However, stratifying the HER2+ group into two subgroups (a) FISH+ and IHC-negative (IHC0 or IHC1+) vs. (b) IHC3+ or ICH2+FISH+ revealed more distinct 11.8 month and 16.0 month median overall survivals, respectively. FISH-positivity alone did not indicate Herceptin benefit; Herceptin benefit was essentially limited to immunohistochemically 3+ gastric cancers or IHC2+ and FISH+ cancers.

IHC or FISH can be used as the first-line testing method, but based on ToGA data and pending future investigations, oncologists should consider immunohistochemistry for optimal frontline testing.