Faculty Bibliography

Molecular markers of ordinary invasive ductal carcinoma of the breast have been extensively studied and their prognostic significance has been assessed. A common variant of breast cancer, tubular carcinoma, has an excellent prognosis as judged from several clinicopathologic studies. One would assume that tubular carcinomas have 'favorable' molecular markers, however, published series of tubular carcinomas do not include molecular markers. We describe the molecular markers of 39 consecutive tubular carcinomas collected between January 1995 and July 1997. DNA ploidy, S-phase, estrogen and progesterone receptor (ER and PR, respectively) expression, and immunoreactivity for MIB-1, p53, and erbB2 were evaluated. Seventy-two percent of tubular carcinomas were DNA diploid, 49% had an S-phase less than 5%, 95% were ER positive, 69% were PR positive, 88% had less than 10% MIB-1-positive cells, 97% were p53 negative, and 97% did not overexpress erbB2 protein. Thus tubular carcinomas exhibit favorable molecular characteristics, which may play a role in their good prognosis

OBJECTIVE: Our objective was to assess our experience in diagnosing pure tubular carcinoma of the breast and to correlate the radiologic and histopathologic features. MATERIALS AND METHODS: A retrospective review of 932 consecutive cases of proven breast cancer diagnosed between 1990 and 1997 revealed 78 cases (8.4%) of tubular carcinoma in 69 patients. Clinical, imaging, cytologic, and histologic findings were analyzed. RESULTS: Mammography revealed tubular carcinoma in 68 (87%) of the 78 cases. Sonography showed tubular carcinoma in all 38 cases in which it was used; nine of these lesions were mammographically occult. These nine lesions were slightly, but not significantly (p < .05), smaller than the 29 lesions that had also been detected on mammography. Large core needle biopsy was performed in 22 patients (sensitivity, 91%). At biopsy, diagnoses were malignant (n = 16 [73%]), suspicious (n = 4 [18%]), atypia (n = 1 [4.5%]), and benign (n = 1 [4.5%]). Fine-needle aspiration biopsy was used to evaluate 36 cases of tubular carcinoma (sensitivity, 50%); cytologic diagnoses were malignant (n = 15 [42%]), suspicious (n = 3 [8%]), atypia (n = 10 [28%]), and benign (n = 8 [22%]). Only 15 (19%) of the 78 tubular carcinomas were palpable. Other tumors were detected within the excised tissue in 47 of the patients (68%); of these other types of lesions, ductal carcinoma in situ was found most often. CONCLUSION: Most cases of tubular carcinoma can be revealed by mammography; for mammographically occult tubular carcinoma, sonography can be performed. The rate of accuracy for determining the presence of tubular carcinoma is higher with large core needle biopsy than with fine-needle aspiration biopsy. Finally, when tubular carcinoma is diagnosed, other histologic types of carcinoma often occur in the same breast

BACKGROUND: The activation of the zymogen plasminogen to the serine protease plasmin by urokinase-type (uPA) and tissue-type (tPA) plasminogen activators (PA) is an important event in a variety of physiologic and pathophysiologic processes in mammals. Enhanced PA activity occurs during angiogenesis and has been correlated in vitro and in vivo with increased tumor aggressiveness and is an indicator of poor prognosis in a variety of tumors in humans. Preliminary studies suggest that the antiulcer drug irsogladine maleate (IM) diminishes PA activity in vitro and may inhibit angiogenesis in vivo. To define the precise mechanism of angiogenesis inhibition by IM in vivo, we tested the ability of IM to blunt angiogenesis in a mouse cornea neovascularization model performed in wild-type and PA-knockout mice. METHODS: Three days prior to pellet implantation, groups of C57Bl/6 wild-type, uPA-deficient (upA-/-), and tPA-deficient (tPA-/-) mice received IM (300 mg/kg), IM (500 mg/kg), or vehicle (0.5% carboxymethylcellulose) via oral gavage. After 3 days of treatment, hydron polymer-coated pellets of sucrose aluminum sulfate containing 100 ng of basic fibroblast growth factor (bFGF) were inserted into surgically created pockets in the cornea of each mouse. On postoperative day 6, the neovascularization of each cornea was evaluated by a blinded observer using slit lamp microscopy and photographed. Angiogenesis was quantified by calculating vascular area (mm2) +/- SEM using a modified formula for a half ellipse that incorporates calibrated vessel measurements [Vessel length (mm) x Clock hours x pi x 0.2]. RESULTS: IM treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3% (P < 0.02, P < 0.001), in tPA-deficient mice by 42.6 and 46% (P < 0.001, P < 0.001), and in uPA-deficient mice by 27.2 and 46% (P < 0.05, p < 0.001), respectively. No quantitative differences in neovascularization were observed in either treatment group between transgenic mouse strains. No toxicity was noted in any group. CONCLUSION: IM inhibits bFGF-induced angiogenesis in wild-type, tPA-knockout, and uPA-knockout mice. The observation that IM significantly diminishes angiogenesis in both PA-deficient mice and wild-type mice suggests that the mechanism of action of IM may be independent of plasminogen activation.