Developing a prognostic index for ductal carcinoma in situ of the breast. Are we there yet?
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Biomarkers, Tumor↗
Biomedical subjects
D N Poller
Publications and source records attributed to D N Poller.
A prognostic index for ductal carcinoma in situ of the breast.
BACKGROUND: There is controversy and confusion regarding therapy for patients with ductal carcinoma in situ (DCIS) of the breast. The Van Nuys Prognostic Index (VNPI) was developed to aid in the complex treatment selection process. METHODS: The VNPI combines three significant predictors of local recurrence: tumor size, margin width, and pathologic classification. Scores of 1 (best) to 3 (worst) were assigned for each of the 3 predictors and then totaled to give an overall VNPI score ranging from 3 to 9. Three hundred thirty-three patients with pure DCIS treated with breast preservation (195 by excision only and 138 by excision plus radiation therapy) were studied with detection of local recurrence as the end point. RESULTS: There was no statistical difference in the 8 year local recurrence free survival in patients with VNPI scores of 3 or 4, regardless of whether or not radiation therapy was used (100% vs. 97%; P = not significant). Patients with VNPI scores of 5, 6, or 7 received a statistically significant 17% local recurrence free survival benefit when treated with radiation therapy (85% vs. 68%; P = 0.017). Patients with scores of 8 or 9, although showing the greatest relative benefit from radiation therapy, experienced local recurrence rates in excess of 60% at 8 years. CONCLUSIONS: DCIS patients with VNPI scores of 3 or 4 can be considered for treatment with excision only. Patients with intermediate scores (5, 6, or 7) show a 17% decrease in local recurrence rates with radiation therapy. Patients with VNPI scores of 8 or 9 exhibit extremely high local recurrence rates, regardless of irradiation, and should be considered for mastectomy.
Breast Neoplasms↗
Intraductal breast carcinoma: experiences from the Breast Center in Van Nuys, California.
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Analysis of Variance↗
C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators.
A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice.
Adult↗
Prognostic classification of breast ductal carcinoma-in-situ.
We present a new prognostic classification designated the Van Nuys classification for ductal carcinoma-in-situ (DCIS). The classification combines high nuclear grade and comedo-type necrosis to predict clinical recurrence. Three groups of DCIS patients were defined by the presence or absence of high nuclear grade and comedo-type necrosis: 1--non-high-grade DCIS without comedo-type necrosis, 2--non-high-grade DCIS with comedo-type necrosis, 3--high-grade DCIS with or without comedo-type necrosis. There were 31 local recurrences in 238 patients after breast-conservation surgery 3.8% (3/80) in group 1, 11.1% (10/90) in group 2, and 26.5% (18/68) in group 3. The 8-year actuarial disease-free survivals were 93%, 84%, and 61%, respectively (all p < or = 0.05). The Van Nuys classification defines three distinct and easily recognisable groups, each of which has a different likelihood of local recurrence if treated with breast conservation.
Bone Neoplasms↗
Cathepsin D in primary breast carcinoma: adverse prognosis is associated with expression of cathepsin D in stromal cells.
The immunohistochemical expression of the aspartyl protease enzyme cathepsin D was examined in a consecutive series of 103 primary operable breast carcinomas with the polyclonal antibody NCL-CDp. Expression of cathepsin D was identified within the epithelial and stromal components of all tumours examined. No significant associations of increased cathepsin D expression in the epithelial tumour component with conventional prognostic indices such as tumour size, grade, lymph node stage, or patient survival were identified. However, significant associations of increased stromal cathepsin D expression and high tumour grade, chi 2 = 11.40 (df = 2), p = 0.003; increased tendency to local recurrence, chi 2 = 6.87 (df = 1), p = 0.009; regional recurrence, chi 2 = 7.44 (df = 1), p = 0.006; poorer disease free survival, chi 2 = 14.9 (df = 1), p = 0.0001; and poorer overall patient survival, chi 2 = 6.90 (df = 1), p = 0.0086, were identified. Cathepsin D expression is present in all breast tumours. Stromal cathepsin D expression is a neglected immunohistochemical prognostic parameter which could explain some of the previous apparently conflicting reports concerning the effect on patient prognosis of biochemical (i.e. total) and immunohistochemical estimations of cathepsin D in breast cancers.
Breast Neoplasms↗
Ten-year results comparing mastectomy to excision and radiation therapy for ductal carcinoma in situ of the breast.
The 10-year results of 300 patients with ductal carcinoma in situ (DCIS) without microinvasion are reported; 167 treated with mastectomy and 133 treated with excision and radiation therapy. There was a significant difference in disease-free survival at 10 years, in favour of those treated with mastectomy, 98% versus 81% (P = 0.0004). Multivariate analysis confirmed nuclear grade as the only significant predictor of local recurrence (P = 0.02) or invasive local recurrence (P = 0.03) in patients with DCIS treated with excision and radiation therapy. There was no difference in breast cancer-specific survival or overall survival between the two treatment groups.
Adult↗
Prostatic discrimination.
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Adenocarcinoma↗
Correlations between the mammographic features of ductal carcinoma in situ (DCIS) and C-erbB-2 oncogene expression. Nottingham Breast Team.
PURPOSE: C-erbB-2 oncogene expression is found in 60% of DCIS cases. C-erbB-2 expression in DCIS has been shown to correlate with comedo subtype, large cell size, lymphoid infiltrate, nuclear pleomorphism, multinucleation and high mitotic rate. These findings have led to the suggestion that the subgroup of DCIS that expresses c-erbB-2 may be a biologically definable category with prognostic significance. The purpose of this study was to identify any differences in the mammographic appearances between DCIS which expresses c-erbB-2 and DCIS that does not express this oncogene. MATERIALS AND METHODS: C-erbB-2 staining characteristics and preoperative mammograms were available for review in 126 patients with pure DCIS. All the mammograms were reviewed by a radiologist knowing the patient had DCIS but without any further pathological or immunohistochemical information. RESULTS: C-erbB-2 positive DCIS showed the following features more commonly than c-erbB-2 negative disease: calcification (65 of 71 (92%) vs 28 of 39 (72%), P < 0.01), ductal distribution of calcification (51 of 65 (78%) vs 16 of 28 (57%), P < 0.05), rod-shaped calcification (53 of 65 (82%) vs 15 of 28 (54%), P < 0.01) and granular calcification (63 of 65 (97%) vs 24 of 28 (86%), P < 0.05). C-erbB-2 negative DCIS more commonly showed an abnormal mammogram without calcification than c-erbB-2 positive disease (11 of 39 (28%) vs 6 of 71 (8%), P < 0.01). CONCLUSION: We have demonstrated significant differences in the mammographic features of c-erbB-2 positive and negative disease. As c-erbB-2 expression has been shown to correlate with aggressive histological features, the differences in the mammographic appearances between c-erbB-2 positive and c-erbB-2 negative DCIS may be of practical value.
Biomarkers, Tumor↗
Screening-detected and symptomatic ductal carcinoma in situ: mammographic features with pathologic correlation.
PURPOSE: To compare the mammographic and pathologic features of screening-detected and symptomatic ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The mammographic and pathologic features of 54 screening-detected and 77 symptomatic cases of DCIS were compared. Patients were aged 30-76 years (mean, 58 years). RESULTS: Diffuse involvement was seen in 10 patients (13%) with symptoms but in none of the screening-detected group (P < .05). The disease was radiologically more extensive in the symptomatic group. Calcifications in the symptomatic group (n = 48) were less likely to have a ductal distribution than those in the screening-detected group (n = 48) (30 [63%] vs 40 [83%], respectively; P < .05). At histologic examination in some cases, the symptomatic group (n = 76) included eight (11%) patients with cribriform-micropapillary, large-cell tumors (P < .05) and less comedocarcinoma (20 [26%] vs 23 [45%], respectively; P < .05) compared with the screening-detected group (n = 51). CONCLUSION: The results show differences in the radiologic and pathologic features of screening-detected and symptomatic DCIS.
Adult↗
Ideas in pathology. Ductal carcinoma in situ of the breast: a proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression.
UNLABELLED: The diagnosis of ductal carcinoma in situ of the breast (DCIS) has become common with the advent of breast screening programs. METHODS: Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumors were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis and morphology. This new classification defines three distinct tumor groups: pure comedo in 19 (25.0%) cases, DCIS with necrosis (non-pure comedo) in 21 (27.6%) patients, and DCIS without necrosis in 36 (47.4%) of cases, the latter group comprising largely classical cribriform or micropapillary architectural subtypes. RESULTS: Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (P < 0.01 [anova]). A preliminary analysis of disease recurrence and disease-free survival in a large series of 391 cases of pure DCIS showed that of 181 cases of pure comedo DCIS there were 19 local recurrences at the 7-year stage (82% 7-year disease-free survival), with 5 local recurrences in 51 cases of DCIS with necrosis (non-pure comedo) (85% 7-year disease-free survival) and only 6 local recurrences in the 159 cases of the DCIS-without-necrosis subgroup (94% 7-year disease-free survival). The chi 2 value for the frequency of disease recurrence of all cases of DCIS with necrosis (i.e., combining the groups of comedo DCIS and DCIS with necrosis (non-pure comedo)) as compared to DCIS without histological evidence of necrosis was 5705 (df = 2; P = 0.0001), and the chi 2 for disease-free survival of types of DCIS with necrosis as compared to cases without necrosis was 178 (df = 2; P = 0.0001). This analysis indicates that the histological presence of necrosis appears to be a relatively powerful predictor of increased disease recurrence and poorer disease-free survival after treatment for DCIS. CONCLUSIONS: Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of more biologically aggressive in situ breast cancer with an intermediate proliferative fraction as compared with the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi 2 analysis. Further larger studies are required to establish if DCIS with necrosis (non-pure comedo) also shows a greater tendency to local recurrence after breast conservation treatment than do subtypes of DCIS without necrosis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in situ mammary carcinoma.
Biomarkers, Tumor↗
p53 protein expression in mammary ductal carcinoma in situ: relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein.
The immunohistochemical expression of the p53 gene protein was examined in a consecutive series of 143 cases of pure ductal carcinoma in situ (DCIS) of the breast. Expression of wild-type and/or mutant p53 protein was detected in 36 (25.2%) of the cases examined, as evidenced by positive nuclear staining with the monoclonal antibody DO 7. Thirty-four (35.8%) of the large cell cases showed p53 protein expression compared with two (4.1%) of the small cell cases (chi 2 = 15.3 [df = 1], P < .001). p53 Protein expression also was associated with an increased histologic degree of necrosis, with a nearly significant association of negative tumor estrogen receptor status and p53 protein expression. No significant association of p53 protein expression and c-erbB-2 protein expression was seen. Immunohistochemical expression of p53 protein is present in approximately 25% of DCIS cases and is confined almost exclusively to large cell DCIS, a morphologic subtype of in situ breast carcinoma thought to be more biologically aggressive. Expression of p53 protein may be important in the neoplastic progression of DCIS, reflecting the acquisition of p53 gene mutations in large cell DCIS cases. Therefore, p53 may be implicated in mammary tumor evolution from in situ to invasive disease.
Biomarkers, Tumor↗
Oestrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein.
The expression of oestrogen receptor protein (ER) was examined in 151 cases of symptomatic or screening detected pure ductal carcinoma in situ (DCIS) of the breast by immunocytochemical assay (ERICA), in formalin-fixed paraffin-embedded tissue, with the monoclonal antibody H 222 (Abbott). Forty-eight tumours (31.8%) of cases were ER positive. Twenty-seven (17.9%) of cases showed high level ER expression and 21 (13.9%) of cases showed low level ER immunoreactivity. Significant associations of positive tumour ER immunoreactivity and non-comedo architecture chi 2 = 6.76; (d.f. = 1): P < 0.001, small cell size chi 2 = 4.49; (d.f. = 1): P = 0.034, higher S-phase fraction chi 2 = 4.71; (d.f. = 1): P = 0.03 and lack of c-erbB-2 protein overexpression chi 2 = 7.96; (d.f. = 1): P < 0.01 were identified. No significant associations of ER expression and patient age, histological grade of necrosis in DCIS, or DNA ploidy were found. ER expression is detectable in less than one third of symptomatic and screening detected cases of DCIS, implying that endocrine therapy of DCIS may be a more appropriate form of management for morphological subtypes of DCIS which show higher rates of oestrogen receptor expression, particularly those of non-comedo and small cell type.
Adult↗
Marking of excision margins of discrete skin lesions.
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Biopsy↗
Oncogenes and tumor morphology prediction.
Oncogenes and oncoproteins have been shown to play an important role in the neoplastic progression of tumors. It is now evident that certain subsets of human tumors show preferential expression of specific oncogenes and oncoproteins that may in turn predict tumor morphology. The phenomenon of preferential oncogene or oncogene protein expression in certain morphologic types of tumor may help to better define the biologic behavior and aggressiveness of a given tumor, so leading to advances in the diagnosis, treatment, and understanding of human neoplasia.
Breast Neoplasms↗
Mural bridging lesions in colonic Crohn's disease.
A case of Crohn's colitis with mural bridging lesions is described. The bridging lesions comprised colonic-type mucosa, smooth muscle, nerve fibers, with foci of adipose tissue and fibrous connective tissue. The lesions arose from the muscularis propria proximal to colonic strictures and possibly due to diverticular outpouching of the colonic wall associated with increased intraluminal pressure, although the exact mechanism of their formation appears unclear. This entity has not been previously described in inflammatory bowel disease, to our knowledge. Bridging pseudopolyps are seen in ulcerative colitis and rarely in Crohn's disease but do not contain substantial amounts of smooth muscle and/or nerve fibers. We believe that the mural bridges described in this article represent residual muscularis propria at the site of diverticular formation due to long-standing Crohn's colitis. We speculate that the stricture formation seen distal to the site of the mural bridging lesions may have been an important factor in formation of the colonic diverticula and, hence, these lesions that we interpret as representing residual muscularis propria adjacent to sites of diverticular formation in long-standing Crohn's colitis.
Adipose Tissue↗
Production and characterization of a polyclonal antibody to the c-erbB-3 protein: examination of c-erbB-3 protein expression in adenocarcinomas.
A polyclonal rabbit antibody was raised to the c-erbB-3 protein using a synthetic peptide corresponding to amino acids 1229-1241 of the predicted protein sequence of c-erbB-3. In Western blot analysis this antibody detects a single band at approximately 165 kD in a c-erbB-3 transfected (293/HER-3) human cell line. c-erbB-3 protein expression was then examined in a variety of adenocarcinomas. Expression of c-erbB-3 protein was indicated by membrane and/or cytoplasmic tumour cell immunoreactivity in formalin-fixed, paraffin-embedded tissue sections. c-erbB-3 protein was detected in a series of 13 out of 14 primary breast carcinomas, 3 of 5 gastric adenocarcinomas, 8 of 9 colonic adenocarcinomas, 2 of 9 prostatic adenocarcinomas, 0 of 6 renal cell carcinomas, 1 of 4 primary lung adenocarcinomas, and 5 of 7 endometrial adenocarcinomas. Immunohistochemical expression of the c-erbB-3 protein appears to be a relatively common event in adenocarcinomas, and further studies are now warranted to establish the role of the c-erbB-3 protein in neoplasia.
Adenocarcinoma↗
p53 protein expression in human breast carcinoma: relationship to expression of epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen receptor.
The expression of p53 protein, oestrogen receptor protein, epidermal growth factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas. Expression of p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical associations of tumour oestrogen receptor positivity and lack of p53 protein expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53 status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases examined) in contrast to other common types of mammary carcinoma. Non-significant trends of p53 protein expression and increased regional tumour recurrence; chi 2 = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f. = 1), P = 0.053 were identified. p53 protein expression is a common event in human breast cancer and is present in both DCIS and invasive mammary carcinoma. Abnormal expression of p53 protein is a feature of both in situ and invasive breast carcinoma, implying that the abnormal p53 protein expression may be implicated in the early stages of mammary carcinoma progression.
Biomarkers, Tumor↗