PATHOLOGY

Basal cell cocktail (34bE12 + p63) improves the detection of prostate basal cells
Zhou M, Shah R, Shen R, Rubin MA
University of Michigan School of Medicine, Ann Arbor, MI
Mod Pathol. 2003; 16: 177A

• Background: High molecular weight cytokeratin (34bE12) and p63 are frequently used as basal cell markers in aid of diagnosis of prostate cancer (PCa). Absence of a basal cell marker in an atypical lesion histologically suspicious for PCa supports a malignant diagnosis. Yet, absence of basal cells by immunohistochemistry (IHC) is not always conclusive. Improving the sensitivity of basal cell IHC is critical to help make diagnostic decisions in conjunction with standard histology. We test the hypothesis that inclusion of both 34bE12 and p63 in a cocktail reaction is advantageous over either marker used alone.
• Design: 1350 benign glands from 9 TURP specimens were use to study the immunostaining intensity and pattern for 34bE12, p63 and the basal cell cocktail. Basal cell marker expression was scored as strong, moderate, weak and negative. Basal cell staining was considered complete if 75% of the gland circumference was positive for the basal cell marker, and partial if 25% of the circumference was stained.
• Results: By IHC, benign glands lack basal cell lining in 2, 6 and 2% of glands with cocktail, 34bE12 and p63 staining, respectively. The staining variance for cocktail is significantly smaller than that for 34bE12 (0.0100 vs. 0.1559, p=0.0008). No significant difference was seen between cocktail and p63 (0.0100 vs. 0.0345, p=0.099). The cocktail stains the basal cell layers more intensely than either 34bE12 or p63 alone, with complete and partial strong basal cell staining in 93 and 1 % of benign glands, compared to 55 and 4% with 34bE12, and 81 and 1% with p63. Complete and partial weak staining is seen in 0 and 0% of benign glands with the cocktail, compared to 8 and 7% with 34bE12 and 4 and 1% with p63 (p=0.007 and 0.014 for cocktail vs. 34bE12 and cocktail vs. p63, respectively). 2.8% of clinically localized PCa had positive 34bE12 staining and 0.3 % had positive p63 staining.
• Conclusions: IHC of the prostatic glands from transition zone is subject to staining variability. 34bE12 is most susceptible, and basal cell cocktail is least susceptible to such variability. Basal cell cocktail not only increases the sensitivity of the basal cell detection, but also reduces the staining variability and therefore renders the basal cell IHC more consistent.
  
• Editorial Comment
  Basal cells are of utmost importance for the diagnosis of adenocarcinoma of prostate. Their presence excludes this diagnosis. Their absence, however, does not mean necessarily that the acinus’s is neoplastic. Most of the times their presence is recognized on hematoxylin and eosin stains. They are located close to the basement membrane, are round, oval or pyramidal and sometimes the nucleus is involved by a clear halo. They are precursors to the secretory cells and not myoepithelial cells.
  In cases of “atypical small acinar proliferation” (ASAP) the presence of basal cells may help a final diagnosis of adenocarcinoma. ASAP is used in cases of “suspicious but not diagnostic of adenocarcinoma”. I prefer this last expression because ASAP may give the impression of an entity or a particular lesion. It only expresses lack of some criteria for the definitive diagnosis of adenocarcinoma.
  In this circumstance the immunostaining for basal cells is critical for the diagnosis. The pathologist uses high molecular cytoqueratins (34bE12) to disclose these cells. Not always this stain is uniform and uncertainty remains as to the correct diagnosis. The cocktail, that is, adding to 34bE12 the p63 seems to improve the efficacy of this immunostaining. We hope that other studies confirm the findings of this paper considering that using 2 antibodies makes the immunostaining more expensive.

Dr. Athanase Billis
Department of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil