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D L Page

Publications and source records attributed to D L Page.

At least 109 records · Page 6Linked to original sources
PubMed1994

Pathology and clinical evolution of ductal carcinoma in situ (DCIS) of the breast.

The therapy of ductal carcinoma in situ is controversial, but is being more and more decided by the pathologic evidence. What we know of the natural history of ductal carcinoma in situ is that the comedo and non-comedo examples seem quite different. As detailed in several reviews, the information from studies following patients after biopsy alone indicate a great difference between the small non-comedo examples of ductal carcinoma in situ and the larger comedo DCIS. The currently available evidence from cases which have been treated by planned surgical excision without radiation therapy would indicate that the non-comedo examples of DCIS may be adequately treated by this modality as indicated in several recent studies.

Breast Neoplasms↗
PubMed1994

Identification of genes expressed in premalignant breast disease by microscopy-directed cloning.

Histopathologic study of human breast biopsy samples has identified specific lesions which are associated with a high risk of development of invasive breast cancer. Presumably, these lesions (collectively termed premalignant breast disease) represent the earliest recognizable morphologic expression of fundamental molecular events that lead to the development of invasive breast cancer. To study molecular events underlying premalignant breast disease, we have developed a method for isolating RNA from histologically identified lesions from frozen human breast tissue. This method specifically obtains mRNA from breast epithelial cells and has identified three genes which are differentially expressed in premalignant breast epithelial lesions. One gene identified by this method is overexpressed in four of five noncomedo ductal carcinoma in situ lesions and appears to be the human homologue of the gene encoding the M2 subunit of ribonucleotide reductase, an enzyme involved in DNA synthesis.

Base Sequence↗
PubMed1994

Long-term risk of breast cancer in women with fibroadenoma.

BACKGROUND: Fibroadenomas are benign breast tumors that are commonly diagnosed in young women and are associated with a slight increase in the risk of breast cancer. These lesions vary considerably in their histologic characteristics. We assessed the correlation between the histologic features of fibroadenomas and the risk of subsequent breast cancer. METHODS: We conducted a retrospective cohort study of a consecutive series of patients with fibroadenoma diagnosed between 1950 and 1968. Follow-up data were obtained for 1835 patients (90 percent of those eligible). Fibroadenomas with cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes were classified as complex. The rate of subsequent breast cancer among the patients was compared with the rates in two control groups, women listed in the Connecticut Tumor Registry and women chosen from among the patients' sisters-in-law. RESULTS: The risk of invasive breast cancer was 2.17 times higher among the patients with fibroadenoma than among the controls (95 percent confidence interval, 1.5 to 3.2). The relative risk increased to 3.10 among patients with complex fibroadenomas (95 percent confidence interval, 1.9 to 5.1) and remained elevated for decades after diagnosis. Patients with benign proliferative disease in the parenchyma adjacent to the fibroadenoma had a relative risk of 3.88 (95 percent confidence interval, 2.1 to 7.3). Patients with a family history of breast cancer in whom complex fibroadenoma was diagnosed had a relative risk of 3.72, as compared with controls with a family history (95 percent confidence interval, 1.4 to 10). Two thirds of the patients had noncomplex fibroadenomas and no family history of breast cancer and did not have an increased risk. CONCLUSIONS: Fibroadenoma is a long-term risk factor for breast cancer. The risk is increased in women with complex fibroadenomas, proliferative disease, or a family history of breast cancer.

Adult↗
PubMed1994

Histologic grading of breast carcinoma. A reproducibility study.

BACKGROUND: A concern with the histologic grading of breast cancer is that tumor grading is a subjective evaluation that may have problems with reproducibility. METHODS: A single slide from 10 invasive breast cancers was submitted to 25 pathologists who practice in six separate groups. Pathologists graded the tumors using a modified Bloom-Richardson (B-R) scheme, and the results were compared. RESULTS: In 8 of the 10 cases, there was greater than 87% agreement by the pathologists as to the final combined B-R grade, with complete agreement in 2 cases. Only one case had any discrepant opinions that ranged from low to high grade, and this involved only 3 of the 25 pathologists. With respect to B-R score, the pathologists tended to score the tumors as either one of two adjacent scores. Due to this clustering, the B-R scheme appears reproducible into five groups: very low and very high grade tumors and B-R score "5,6," "6,7," and "7,8" tumors. This clustering was especially noticeable in two cases with split decisions, in which the discrepancy in final combined grade was largely due to the tumors being given B-R scores that straddled and were then condensed into two B-R grades. A consensus from each pathology group tended to merge with the majority opinion of all 25 pathologists and was correct for outliers. CONCLUSIONS: This study indicates that reproducibility of grading breast cancers can be achieved when a histologic grading scheme with specified guidelines is used. Pathologists must be aware of the limits of reproducibility, with appropriate guidelines being followed to help optimize agreement, and there should be an awareness of how pathologists group in their evaluations. Also, it may be advisable to better correlate or link reproducibility data with prognostic data in the design of grading schemes.

Breast Neoplasms↗
PubMed1994

Heterogeneous expression of nm23 gene product in noninvasive breast carcinoma.

BACKGROUND: The two major types of noninvasive breast carcinoma, ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS), are quite different in their histopathologic appearance and clinical implications. LCIS is only a marker of an increased risk of later development of invasive carcinoma, whereas most DCIS lesions are at least nonobligate precursors of invasive carcinoma. DCIS is a heterogeneous group of lesions composed of several distinct subtypes, with only the comedo subtype having immediate malignant potential. The authors' purpose was to analyze noninvasive carcinomas for the presence of a gene product (nm23) indicative of a favorable prognosis in invasive carcinomas to determine differences (1) among the different types of CIS and (2) in CIS with and without an accompanying invasive component. METHODS: Immunohistochemical methods were used to detect nm23 gene product in archival material from two groups of patients: Group 1 consisted of 54 cases of purely noninvasive carcinoma, and Group 2 consisted of 55 examples of noninvasive carcinoma associated with an invasive component. RESULTS: Among the cases of CIS with no invasion, LCIS and comedo DCIS expressed more nm23 than noncomedo DCIS (P < or = 0.03). There were no differences among these CIS subtypes in the group with invasion. Comparing subtypes of CIS in the groups with or without invasion, only comedo DCIS was significantly different, with greater expression in the CIS group with no invasion compared with comedo DCIS associated with an invasive component (P = 0.04). CONCLUSIONS: These results support the special nature of LCIS and the heterogeneous nature of DCIS. The in situ component attending an invasive component may be different from anatomically similar lesion without associated invasion. The absence of nm23 in comedo DCIS may be indicative of invasive capacity.

Adult↗
PubMed1994

Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions.

BACKGROUND: The increased prevalence of ductal carcinoma in situ (DCIS) has produced a growing awareness of the importance of its diverse patterns. These differences in pattern have become clinically significant as predictive indicators of success for planned local excisions of small DCIS lesions. METHODS: The authors reviewed 100 sequentially collected DCIS cases from a consultation practice. Recognizing the bias of such a series toward exclusion of easily recognizable comedo DCIS, the authors investigated the spectrum of mixed pattern lesions to identify variations and common features in the architectural arrangement of the various histologic patterns. RESULTS: Patterns of atypical ductal hyperplasia (ADH) with specific criteria of recognition were intermixed in 17 cases (11 cribriform, 1 solid, 1 micropapillary, 4 mixed). Thirty-three cases of DCIS consisted of mixed patterns of comedo and noncomedo types. No case of comedo DCIS with associated areas of ADH was identified. In all cases of combined DCIS and ADH, the more advanced patterns of DCIS were present in the central portion of the lesion, with the ADH components arranged peripherally. This tendency for the more severely atypical areas to be located centrally was present throughout the study. CONCLUSIONS: Different patterns of DCIS are frequently present within individual lesions (46 of 100), and the more advanced features of architectural atypia are regularly present centrally. This strongly supports the hypothesis that these lesions develop from a central focus and expand peripherally. Also, those lesions with low-grade DCIS at the periphery may be as amenable to local excision for cure as purely low-grade lesions.

Adenocarcinoma↗
PubMed1994

Effects of group B Streptococcus toxin on long-term survival of mice bearing transplanted Madison lung tumors.

GBS toxin is a polysaccharide exotoxin produced by group B Streptococcus. This organism causes sepsis and respiratory distress in human neonates (so-called early onset disease). This disease is marked by a strong inflammatory response only in the lung, with pulmonary sequestration of granulocytes and extensive capillary endothelial damage, and occurs only during the first few days after birth. We have found that a similar inflammatory response can be induced by i.v. infusion of picomole quantities of GBS toxin in the developing vasculature of transplanted tumors in mice and can significantly retard the tumor growth. When optimum treatment with GBS toxin was started shortly after tumor implantation, a majority of tumors in the mice regressed and the mice remained tumor-free for over 5 months. Some tumors regressed in mice receiving short-term treatment with GBS toxin, but recurred after the treatment was stopped. Median survival times were extended by all regimens and all doses of GBS toxin tested. No evidence of toxicity to the vasculature of other tissues was observed. GBS toxin is being tested for cancer therapy in humans.

Adenocarcinoma↗
PubMed1994

Ductal carcinoma in situ of the breast with apocrine cytology: definition of a borderline category.

Papillary patterns of apocrine cells are frequent in benign breast biopsies and pose little diagnostic difficulty when the classic apocrine cytology is present. Dilemmas in diagnosis do occur, however, when the usual papillary patterns of hyperplastic apocrine epithelium are absent in hyperplastic lesion, particularly if it is extensive, presents more complex patterns, and/or lacks usual nuclear features. We classified lesions with nonclassic apocrine features into diagnostic categories to separate those with malignant potential from those that are truly benign. We selected 54 such cases sent in consultation over a 2-year period (1989 to 1991). We applied two sets of criteria: nuclear patterns (usual, borderline, and as seen in ductal carcinoma in situ) and extent of lesion (< mm, 4 to 8 mm, and > 8 mm). The cases were categorized into diagnostic groups defined by these criteria of extent of lesion and cytologic features. We believe that application of these criteria recognizing borderline features to unusual, apocrine lesions fosters reproducibility in diagnosis and thus predictability of clinical outcome. We found only 10 cases to fit into borderline categories after use of the two criteria. The clinical utility of this suggested diagnostic stratification will require follow-up studies for linkage of criteria to clinical outcomes.

Breast Neoplasms↗
PubMed1994

Pathology of preinvasive and excellent-prognosis breast cancer.

Concern about the recognition of especially good prognoses continues to be resolute among those who decide, with patients, the course of treatment. Prognostic considerations are paramount in this planning process, and should emphasize precision in case definition and repeated verification in comparable studies. Excellent-prognosis invasive lesions, subtyping of ductal carcinomas in situ, and premalignant indications within otherwise benign breast biopsy specimens are highlighted in this review.

Adult↗
PubMed1994

Status of breast cancer prognostication based on histopathologic data.

The authors present the current status of histopathologic data for prognostication in breast cancer. Current guidelines for using the combined histologic grade are given, as is a review of clinical settings in which this robust grading system has been proved predictive. Precise guidelines are also presented for recognizing special histologic types of cancer, which are associated with an excellent prognosis. Histopathologic methods for assessing cellular proliferation are also presented. This is a dynamic time in the field of breast histopathology when there is a wider and widening appreciation for the clinical utility of these assessments. Concurrently, these approaches should be used with care and clinical relevance of this information should be presented with clarity.

Breast Neoplasms↗
PubMed1994

Medullary carcinoma is associated with expression of intercellular adhesion molecule-1. Implication to its morphology and its clinical behavior.

The histological hallmarks for the diagnosis of medullary breast cancer are circumscription, syncytial architecture, diffuse inflammatory infiltrate, and highly atypical nuclei. The biological and prognostic implication is a lower propensity to metastasize. We studied 19 medullary carcinomas for expression of the intercellular adhesion molecule-1 and lymphocyte-function-associated antigen-1, Neu differentiation factor, tumor necrosis factor-alpha, and the expression of HER-2/neu, HER-4, and HER-3 receptors. Our study revealed that all of the 19 medullary carcinomas expressed the intercellular adhesion molecule-1 and lymphocyte function associated antigen. Eighteen of 19 cancers expressed Neu differentiation factor and tumor necrosis factor-alpha. All medullary cancers expressed the HER-2/neu receptor, however, in the majority of the cases, the staining was confined to the cytoplasm. Only 4 of 12 cancers expressed HER-4 and none of the eight medullary cancers tested expressed HER-3. By comparison, in a control group of infiltrating ductal carcinomas, expression of intercellular adhesion molecule-1, lymphocyte function associated antigen-1, and Neu differentiation factor was positive in about 25 to 30% of the cases, HER-4 was expressed in 75% and HER-3 in 95% of the cases. Taken together, our observations suggest that the expression of intercellular adhesion molecule-1, lymphocyte function associated antigen, Neu differentiation factor, and tumor necrosis factor-alpha as factors that may affect the special morphology and the biological behavior that characterizes medullary carcinomas.

Breast Neoplasms↗
PubMed1994

Pathology and heredity of breast cancer in younger women.

The pathology of early-age onset breast cancer is considered here from three perspectives: 1) benign proliferative disease, 2) the cancers themselves, and 3) familial and hereditary breast cancer. Hereditary breast cancer, a subset of familial breast cancer featuring a strong autosomal dominant pedigree pattern and multiple primary cancers, has a strong predilection for younger women, accounting for about one half of breast cancers under age 30. With respect to benign proliferative disease, the increased relative risk of breast cancer associated with proliferative disease with atypia, about fourfold to fivefold for all ages, is doubled by the presence of a family history of breast cancer and amplified by young age. With respect to the carcinomas, the relative incidences of medullary carcinoma and ductal carcinoma in situ are increased in young women, while lobular and tubular carcinomas are decreased. Invasive breast cancer is higher grade and more proliferative in younger women, as measured by thymidine-labeling index, DNA flow cytometric S-phase fraction, and proliferation-associated proteins. The increased fraction of ductal carcinoma in situ and higher grade invasive cancers may help to account, respectively, for increased recurrence rates with conservative therapy, and more aggressive natural history in younger women. Familial breast cancers show trends for increased medullary type, but the effect is not independent of age. Weak associations of family history with tubular carcinoma have been reported, but data for associations with lobular carcinoma in situ and invasive lobular carcinoma are conflicting. Hereditary breast cancer as a class has higher tumor proliferation rates, an effect independent of age. Knowledge of the pathology and biomarker characteristics of BRCA1 gene-linked hereditary breast cancers, which account for a substantial fraction of breast cancers in younger women, should shed light on the nature of the responsible gene(s) and guide approaches to therapy and prophylaxis.

Adult↗
PubMed1994

p53 mutations are confined to the comedo type ductal carcinoma in situ of the breast. Immunohistochemical and sequencing data.

BACKGROUND: Mutations in the p53 tumor suppressor gene have been identified in breast and many other carcinomas. It is not clear, however, when these mutations occur during breast carcinogenesis. Overexpression of 53 protein has been reported in some ductal carcinoma in situ (DCIS) lesions. To further study the overexpression of p53 in DCIS of the breast and correlate these findings with changes at the molecular level, we performed p53 immunostaining and direct sequencing in noncomedo and comedo DCIS. EXPERIMENTAL DESIGN: Archival blocks were obtained on cases of noncomedo DCIS, (including encysted, noninvasive papillary carcinoma) and comedo DCIS. Immunohistochemical staining with the p53 antibody DO7 was performed on all cases. Polymerase chain reaction (PCR) amplification of exons 5, 6, and 7 of the p53 gene was performed and the PCR products were directly sequenced. Four comedo DCIS cases that were p53 immunopositive were further screened for p53 mutations by PCR/single strand conformation polymorphism in exons 8 and 9 of the p53 gene. One of these cases showing a mobility shift was directly sequenced. RESULTS: We examined 39 lesions including comedo DCIS (N = 12) and noncomedo DCIS (N = 27), the latter including 17 encysted noninvasive papillary carcinomas. Immunostaining with DO7 was positive in 4 of 12 comedo DCIS lesions (33%) while all noncomedo lesions including encysted noninvasive papillary carcinomas were negative. Direct sequencing of PCR products confirmed wild-type DNA in exons 5 and 6 in all noninvasive papillary carcinomas, 3 randomly selected noncomedo DCIS lesions, and 4 p53 antibody-positive comedo DCIS lesions. In these latter 4 cases, wild-type DNA sequences were preserved in exon 7 for all cases. A single case had a conformational shift in exon 8 within the four cases screened in exons 8 and 9. Direct DNA sequencing of this exon revealed a G to A point mutation resulting in an arginine-to-histidine substitution at codon 273 of the protein. CONCLUSIONS: Our results suggest that mutant p53 protein accumulation in preinvasive lesions is limited to comedo (high grade) DCIS and that p53 positivity by immunohistochemistry does not correlate in all cases with specific p53 mutations in exons 5 to 9, the most highly conserved regions of this gene.

Aged↗