Topoisomerase II␣ (topo II␣) plays a key role in DNA replication and is a target for multiple chemotherapeutic agents. In breast cancer, topo II expression has been linked to cell proliferation and HER2/ neu protein overexpression. However, its relationship with outcome variables is not well established.Formalin-fixed, paraffin-embedded primary breast cancers from 184 women (mean age, 60 years) were stained for topo II by automated immunohistochemistry. A topo II expression index ( Topoisomerase II␣ (topo II␣) is a component of the DNA machinery that is intricately involved at many levels of DNA metabolism (1-3). Its primary function is to alter DNA topology from its storage (supercoiled) form to a more exposed (partially uncoiled) form by inducing single-strand DNA breaks and simultaneously passing another intact double helix through the gap (4 -5). The anthracycline class of antitumor cytotoxic drugs is topoisomerase poisons specifically targeting topo II␣ (2, 6 -7). These drugs create a cleavable complex including drug, topo II␣, and DNA strand. It is hypothesized that the cleavable complex damages the DNA, causing toxicity, and may induce apoptosis in proliferating tumor cells (8 -10). From most in vitro analyses, it has been shown that low levels of topo II␣ expression in cancer cells are associated with drug resistance, whereas high levels indicate sensitivity (11-13). However, in one study, no correlation between the level of topo II␣ expression and drug sensitivity in breast cancer cell lines was found (14), and recent reports using paraffinembedded breast cancer tissues failed to find associations between topo II␣ expression and drug sensitivity (15).

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Inflammation of ileal reservoir mucosa ("pouchitis") is a common sequelae in ulcerative colitis (UC) patients who have had a colectomy with ileal pouch anal-anastomosis (IPAA). Although several clinical, genetic, and laboratory parameters have been evaluated, reliable pathologic predictors for the development of pouchitis are lacking. The purpose of this case-control study was to determine whether there are any pathologic features in UC colectomy specimens that may help predict the subsequent development of pouchitis after an IPAA procedure. The study group consisted of 39 UC patients (male/female ratio: 21/18, mean age: 35 years), who had at least 1 episode of pouchitis after an IPAA procedure during the follow-up period (mean: 57 months, range: 12-121 months). There were 26 control patients (male/female ratio: 11/15, mean age: 37 years), all of whom also underwent a total colectomy and IPAA procedure for UC, but did not develop pouchitis during the follow-up period (mean: 78 months, range: 14-223 months). Routinely processed tissues from each colectomy specimen were evaluated for a variety of histologic features, such as extent of colitis, severity of colitis, extent of severe colitis, type and extent of ulceration, presence and severity of appendiceal inflammation, and the presence of active ileitis, and compared between the study and control patients. Pathologic features that were associated with the subsequent development of pouchitis included the presence of severe colitis that extended into the cecum (severe pancolitis), which was present in 7/39 (18%) pouchitis patients, but in none (0%) of the control patients (P = 0.03), early fissuring ulcers [9/39 (23%) pouchitis cases versus 1/26 (4%) controls (P = 0.04)], active inflammation of the appendix [20/32 (63%) pouchitis patients versus 7/19 (31%) controls (P = 0.03)], and appendiceal ulceration [13/32 (41%) pouchitis patients versus none (0%) of the controls (P = 0.002)]. No significant differences in patient gender or age, depth or extent of ulceration, or the presence or absence of "backwash ileitis" were identified between the 2 groups. In conclusion, there are several histologic features in colectomy specimens from UC patients who have undergone an IPAA procedure that may help predict the subsequent development of pouchitis. Of these features, appendiceal ulceration is highly associated with pouchitis.