Although numerous studies have reported that high frequencies of loss of heterozygosity (LOH) at various chromosomal arms have been identified in breast cancer, differential LOH in the neoplastic epithelial and surrounding stromal compartments has not been well examined. Using laser capture microdissection, which enables separation of neoplastic epithelium from surrounding stroma, we microdissected each compartment of 41 sporadic invasive adenocarcinomas of the breast. Frequent LOH was identified in both neoplastic epithelial and/or stromal compartments, ranging from 25 to 69% in the neoplastic epithelial cells, and from 17 to 61% in the surrounding stromal cells, respectively. The great majority of markers showed a higher frequency of LOH in the neoplastic epithelial compartment than in the stroma, suggesting that LOH in neoplastic epithelial cells might precede LOH in surrounding stromal cells. Furthermore, we sought to examine pair-wise associations of particular genetic alterations in either epithelial or stromal compartments. Seventeen pairs of markers showed statistically significant associations. We also propose a genetic model of multi-step carcinogenesis for the breast involving the epithelial and stromal compartments and note that genetic alterations occur in the epithelial compartments as the earlier steps followed by LOH in the stromal compartments. Our study strongly suggests that interactions between breast epithelial and stromal compartments might play a critical role in breast carcinogenesis and several genetic alterations in both epithelial and stromal compartments are required for breast tumour growth and progression.

The purpose of this study was to determine the diagnostic utility of helical computed tomography (CT) for the diagnosis of ectopic ureters in the dog and to compare these findings with those of digital fluoroscopic excretory urography and digital fluoroscopic urethrography. Ureteral ectopia was confirmed or disproved based on findings from cystoscopy and exploratory surgery or post-mortem examination. Of 24 dogs (20 female, 4 male) evaluated, 17 had ureteral ectopia. Digital fluoroscopic excretory urography and CT correctly identified ureteral ectopic status and site of ureteral ectopia (P .05). Urethrography did not reliably detect ureteral ectopia. No false-positive diagnoses of ureteral ectopia were made in any of the imaging studies. Cystoscopic findings significantly agreed with findings during surgery in determining ureteral ectopic status and ectopic ureter site. One false-positive cystoscopic diagnosis of unilateral ureteral ectopia was made in a male dog. Kappa statistics showed better agreement between CT and both cystoscopy and surgical or postmortem examination findings with regard to presence and site of ureteral ectopia compared with other imaging techniques. CT was more useful than other established diagnostic imaging techniques for diagnosing canine ureteral ectopia.

The ability of computed tomography (CT) to distinguish malignant from nonmalignant splenic masses was evaluated in 21 dogs with 24 masses. CT scans of the abdomen were performed pre- and postintravenous contrast medium administration before splenectomy or euthanasia. Splenic masses were evaluated objectively based on Hounsfield units (HU) and volume. Subjective criteria included location within the spleen (head, body, or tail), margination, homogeneity, and attenuation compared to the remaining splenic parenchyma. Characteristics of malignant and nonmalignant masses were compared. The nonmalignant masses were divided into splenic hematomas and nodular hyperplasia for further analysis. Fourteen (58.3%) of the masses were nonmalignant; 10 (41.7%) were malignant. Malignant splenic masses had significantly lower attenuation values, measured in HU, than nonmalignant splenic masses, on both pre- and postcontrast images (P<0.05). On postcontrast images, there was a significant difference in attenuation characteristics among all three subsets of splenic masses (malignant, hematoma, hyperplasia), with nodular hyperplasia having the highest HU values (90.3), hematomas having intermediate HU values (62.5), and malignant splenic masses having the lowest HU values (40.1). A receiver operator characteristic curve of postcontrast medium HU values revealed 55 as the best threshold value to distinguish malignant from nonmalignant masses, with those less than the threshold value being malignant. Abdominal CT is a useful diagnostic imaging modality for evaluation of focal canine splenic masses, with a significant difference in imaging characteristics between malignant and nonmalignant masses.

Primary malignant melanomas of the squamous mucosa of the head and neck are rare. To learn more about the prognostic significance of various histologic parameters we examined the pathologic features of squamous mucosa from 40 patients seen at a single institution and correlated them with clinical outcome. Follow-up information was available on 37 patients. Thirty-five were treated with surgical resection and two were treated with radiotherapy. Twenty-six were dead at follow-up. Twenty-one of them died of disease. The interval between diagnosis and death ranged from 1 month to 16.5 years (median survival, 2.4 years). Eleven patients were alive at 4 months to 19.5 years after the diagnosis: six of them with disease and five of them free of disease (mean follow-up, 3.5 years). Predictors of poor survival by univariate analysis were the presence of vascular invasion (overall survival, p = 0.007; disease-specific survival, p = 0.01), a polymorphous tumor cell population (overall survival, p = 0.007; disease-specific survival, p = 0.008), and necrosis (overall survival, p = 0.007; disease-specific survival, p = 0.056). However, because these three parameters were associated with each other, none of them remained of independent predictive value for outcome by multivariate analysis. No prognostic significance was found for tumor thickness, level of invasion, ulceration, mitotic index, or nerve/nerve sheath involvement. Thus, the histologic parameters relevant for the prognosis of squamous mucosa differ significantly from those of cutaneous melanomas.