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R Kandel

Publications and source records attributed to R Kandel.

At least 19 recordsLinked to original sources
PubMed2006

Cyclin D1 and p21 is elevated in the giant cells of giant cell tumors.

Alterations of cell cycle regulatory proteins, especially those that regulate G1 to S transition, have been implicated in the pathogenesis of a wide variety of human tumors. In previous studies we showed that that there is overexpression of cyclin D1 protein predominately in the giant cell component of giant cell tumors of bone. The purpose of this study was to investigate the mechanisms that may be responsible for cyclin D1 accumulation in giant cell tumors. Giant cell tumors have high levels of cyclin D1 mRNA and the giant cell-enriched population of these tumors have significantly more mRNA and protein expression of cyclin D1 than the mononuclear cell population. The giant cells also expressed higher levels of p21 protein and more p21 bound to cyclin D1 than the mononuclear cells. It is possible that p21 may be contributing to the cyclin D1 accumulation that occurs in the giant cells and perhaps even giant cell formation in these tumors. Additional studies are required to confirm the role of p21 in the pathogenesis of these tumors.

Bone Neoplasms↗
PubMed2005

Transarticular invasion of bone tumours across the sacroiliac joint.

PURPOSE: The purpose of this study was to evaluate the pattern of tumour spread across the SI articulation, correlating with cadaveric anatomic observations, in order to better understand the local spread of tumour and to assist in the assessment of local staging. MATERIAL AND METHODS: Twenty-four consecutive patients (14 male, 10 female; age range 22-89 years, mean 52 years) with primary bone tumours of the iliac bone or sacrum abutting the SI joint, in whom surgical resection of the SI joint was performed, were studied following institutional ethics approval. In all patients, preoperative magnetic resonance (MR) imaging studies of the pelvis and SI joint were reviewed for imaging evidence of transarticular extension across the SI joint. Gross pathologic and histologic assessment of possible transarticular SI joint tumour extension was performed in all patients. Nine cadaveric pelvic specimens without pelvic neoplastic disease (4 male, 5 female; age range 20-84 years, mean 59 years, median 58 years) were anatomically dissected and the articular anatomy of the SI joint examined macroscopically. RESULTS: Twelve of the twenty-four patients demonstrated imaging and histological evidence of transarticular SI joint invasion. Eight tumours infiltrated only the interosseous ligamentous aspect of the SI joint. In the remaining four cases, extensive tumour infiltrated both the cartilaginous and ligamentous aspects of the joint. No case showed tumour involvement isolated to the cartilaginous aspect of the joint. Among the cadaveric specimens studied, degenerative changes were found involving the majority of cases (6/9), with cartilage thinning and fibrillation and antero-superior marginal osteophytes seen involving the cartilaginous portion of the SI joint articulation. Four of the nine specimens demonstrated central ossification bridging the iliac and sacral aspects of the ligamentous (interosseous) SI joint. CONCLUSION: Tumour invasion across the SI articulation favours its interosseous ligamentous portion. Factors influencing transarticular tumour extension and its preferential course across the interosseous component of the articulation have been discussed. It is particularly important to assess the interosseous ligamentous portion of the SI articulation when locally staging primary pelvic bone tumours subjacent to the SI articulation, as this will have a significant impact on planning surgical management.

Adult↗
PubMed2004

Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy.

INTRODUCTION: Trace elements are known to influence bone metabolism; however, their effects may be exacerbated in renal failure because dialysis patients are unable to excrete excess elements properly. Our study correlated bone quality in dialysis patients with levels of bone fluoride, magnesium, and aluminum. A number of studies have linked trace elements, including fluoride, magnesium, and aluminum, to the development of renal osteodystrophy (ROD). However, little is known about the relationship between trace elements and changes in bone quality in ROD patients. The purpose of this study was to examine bone quality in ROD patients, and correlate differences in bone quality to trace element concentrations in bone. Bone quality encompasses parameters that contribute to the mechanical integrity of the bone. METHODS: One hundred fifty-three anterior iliac crest bone biopsies from patients with ROD were examined and subdivided into five groups based on the pathological features. Parameters contributing to bone quality, such as bone structure and remodeling, connectivity, mineralization, and microhardness, were assessed and correlated to bone chemical composition. In addition, clinical symptoms of ROD were assessed and correlated with bone composition. RESULTS AND CONCLUSIONS: There were no differences in bone architecture between the different ROD bone groups; however, differences in bone mineralization and microhardness were observed. Increase in bone fluoride was associated with increased osteoid parameters and decreased bone microhardness. Bone mineralization and microhardness decreased with increasing bone magnesium content and intact parathyroid hormone (PTH) level. Moreover, bone magnesium increased with intact PTH levels. The relationship between PTH, bone magnesium, mineralization, and microhardness was primarily observed in aplastic bone disorder. Furthermore, bone magnesium and aluminum contents were positively associated with bone pain and proximal myopathy in these patients. Most importantly, fluoride, magnesium, and aluminum showed significant correlations with one another. These results suggested that in ROD, bone fluoride may diminish bone microhardness by interfering with mineralization. Magnesium may be involved in the suppression of PTH secretion, lowering bone turnover thus leading to an increase in bone mineralization profile and microhardness in aplastic bone disorder. The effects of fluoride and magnesium on bone quality may be exacerbated by their interaction with aluminum.

Aluminum↗
PubMed2002

Characterisation of reconstituted equine cartilage formed in vitro.

Lesions in cartilage of equine weightbearing joints commonly result in lameness. Cell-based resurfacing techniques are currently being developed for human and veterinary applications. Biopsies of stifle joint cartilage (1 g) were harvested aseptically and chondrocytes were isolated by sequential enzyme digestion. The cells were grown in vitro on filter inserts. Analysis of cultures 8 weeks later showed that the cells had accumulated extracellular matrix and formed a continuous layer of cartilagenous tissue as determined histologically. The cells maintained their phenotype as they synthesised type II collagen and proteoglycans similar in size to those synthesised by chondrocytes in native cartilage, but this reconstituted tissue had more sulphated glycosaminoglycan and lower collagen content than native cartilage. This experiment tests the feasibility of growing equine cartilagenous tissue in vitro. This tissue may be useful in the management of chondral injuries in the horse in a scenario where the patient donates cells, the cells are propagated under laboratory conditions and the resulting tissue becomes the therapeutic agent.

Animals↗
PubMed2001

Cyclin D1 protein overexpression and gene amplification in benign breast tissue and breast cancer risk.

Cyclin D1 amplification and/or protein overexpression have been observed not only in breast cancer but also in the putative early stages of breast neoplasia. In a case-control study nested within a cohort of 4888 women, we investigated whether the occurrence of cyclin D1 gene amplification and/or protein overexpression in benign breast tissue might identify women at increased risk of subsequent breast cancer development. Cases were 92 women with a histological diagnosis of benign breast disease who subsequently developed breast cancer. Five controls (women with benign breast disease who had not developed breast cancer by the date of diagnosis of the corresponding case) were selected randomly for each case from those non-cases available within strata defined by screening centre, National Breast Screening Study (NBSS) study arm, year of birth and age at diagnosis of benign breast disease. Paraffin blocks of benign tissue were suitable for immunostaining for 71 cases and 293 controls. Sufficient DNA for analysis was obtained from a total of 356 subjects (69 cases, 287 controls). The benign breast tissues and breast cancers were immunostained for cyclin D1 and also analysed for the presence of cyclin D1 gene amplification by differential polymerase chain reaction (PCR). Fifteen cases and 60 controls showed evidence of cyclin D1 immunostaining, and 12 cases and 29 controls showed cyclin DL gene amplification. There was essentially no association between cyclin D1 protein overexpression in benign breast tissue and risk of subsequent breast cancer (adjusted odds ratio (OR) 1.06; 95% confidence interval (CI) 0.56-2.02). After adjustment for potential confounding, there was a statistically non-significant 40% increase in risk of breast cancer in association with cyclin D1 gene amplification (adjusted OR 1.41; 95% CI 0.62-3.22). As multiple genetic changes are required to develop breast cancer, it may not be until the cascade of molecular alterations leading to breast cancer development is understood that identification of biomarkers of breast cancer risk will be possible.

Adult↗
PubMed2001

Prophylaxis and treatment of influenza virus infection.

Influenza virus infections remain an important cause of morbidity and mortality. Furthermore, a recurrence of pandemic influenza remains a real possibility. There are now effective ways to both prevent and treat influenza. Prevention of infection is most effectively accomplished by vaccination. Vaccination with the inactivated, intramuscular influenza vaccine has been clearly demonstrated to reduce serious morbidity and mortality associated with influenza infection, especially in groups of patients at high risk (e.g. the elderly). However, the inactivated, intramuscular vaccine does not strongly induce cell-mediated or mucosal immune responses, and protection induced by the vaccine is highly strain specific. Live, attenuated influenza vaccines administered intranasally have been studied in clinical trials and shown to elicit stronger mucosal and cell-mediated immune responses. Live, attenuated vaccines appear to be more effective for inducing protective immunity in children or the elderly than inactivated, intramuscular vaccines. Additionally, novel vaccine methodologies employing conserved components of influenza virus or viral DNA are being developed. Preclinical studies suggest that these approaches may lead to methods of vaccination that could induce immunity against diverse strains or subtypes of influenza. Because of the limitations of vaccination, antiviral therapy continues to play an important role in the control of influenza. Two major classes of antivirals have demonstrated ability to prevent or treat influenza in clinical trials: the adamantanes and the neuraminidase inhibitors. The adamantanes (amantadine and rimantadine) have been in use for many years. They inhibit viral uncoating by blocking the proton channel activity of the influenza A viral M2 protein. Limitations of the adamantanes include lack of activity against influenza B, toxicity (especially in the elderly), and the rapid development of resistance. The neuraminidase inhibitors were designed to interfere with the conserved sialic acid binding site of the viral neuraminidase and act against both influenza A and B with a high degree of specificity when administered by the oral (oseltamivir) or inhaled (zanamivir) route. The neuraminidase inhibitors have relatively low toxicity, and viral resistance to these inhibitors appears to be uncommon. Additional novel antivirals that target other phases of the life cycle of influenza are in preclinical development. For example, recombinant collectins inhibit replication of influenza by binding to the viral haemagglutinin as well as altering phagocyte responses to the virus. Recombinant techniques have been used for generation of antiviral proteins (e.g. modified collectins) or oligonucleotides. Greater understanding of the biology of influenza viruses has already resulted in significant advances in the management of this important pathogen. Further advances in vaccination and antiviral therapy of influenza should remain a high priority.

Amantadine↗
PubMed2001

Periosteal chondroid tumors: radiologic evaluation with pathologic correlation.

OBJECTIVE: The purpose of this study was to determine whether the imaging features of periosteal chondroid tumors correlate with histopathology. MATERIALS AND METHODS: Twenty-two patients (nine women and 13 men; mean age, 33 years) with pathologically proven periosteal chondroid lesions were retrospectively reviewed. The imaging modalities included conventional radiography (n = 17), CT (n = 10), and MR imaging (n = 14). The images were reviewed by two osteoradiologists, with agreement by consensus. Evaluation criteria included lesion location, mineralization, and size; periosteal reaction; and cortical response. Intramedullary extension, adjacent intramedullary edema, soft-tissue edema, and intrinsic characteristics were also evaluated on MR imaging. After the evaluation, a radiologic diagnosis of chondroma or chondrosarcoma was obtained. An experienced osteopathologist who was unaware of the patient's medical history and radiologic findings reviewed all histopathology. Agreement between the radiologic and the histopathologic diagnosis was tested using the kappa analysis. Imaging features were correlated with the pathologic findings, and a statistical analysis was performed. RESULTS: Using strict pathologic criteria, we diagnosed 11 chondromas and 11 chondrosarcomas (nine, grade I; two, grade II). Moderate agreement was reached between the radiologic and the pathologic diagnosis (kappa = 0.55). The size of periosteal chondrosarcomas (range, 3-14 cm; median, 4 cm) was considerably larger than the size of the chondromas (range, 1-6.5 cm; median, 2.5 cm; p < 0.05). Other imaging features did not significantly correlate with benign versus malignant disease at pathology (all p > 0.05). CONCLUSION: A variable overlap existed in the imaging appearances of benign and malignant periosteal chondroid lesions, with size being the most reliable indicator in distinguishing the two lesions. This and the fact that histologic differentiation of the entities can be difficult, suggests that surgical wide excision may be the most appropriate procedure in treating patients with lesions greater than 3 cm.

Adult↗
PubMed2000

p53 protein accumulation and mutations in normal and benign breast tissue.

Mutations in the p53 gene are amongst the most common molecular changes detected in breast cancer, and there are several reports suggesting that changes in p53 may contribute to the pathogenesis of this disease. In a previous case-control study, we demonstrated that p53 protein accumulation detected by immunohistochemistry in normal or benign breast tissue was associated with a 2.5-fold increase in the risk of subsequent breast cancer. In this study, we investigated whether p53 gene mutations were present in the 29 p53 immunopositive normal or benign breast tissue samples and in 15 p53 immunonegative normal or benign breast tissue samples selected randomly from the original study. DNA was extracted from paraffin sections and underwent PCR-SSCP analysis for exons 4 to 10. PCR products that showed abnormal mobility were excised and sequenced. Sixteen (59.2%) of the 27 immunopositive breast tissue samples and 4 (26.7%) of the 15 immunonegative samples had p53 sequence changes. There was no obvious association between the occurrence of these alterations and any specific histopathologic features. Ten cases showed p53 mutations, and they were all missense base substitutions of the transition type. Thirteen other gene changes occurred in 11 breast tissue samples and consisted of 8 silent (no amino acid change), 4 intronic alterations, and 1 indeterminate alteration. One individual had both a mutation and a silent change. In summary, p53 gene alterations can occur in normal or benign breast tissue, but resolution of their role in the pathogenesis of breast cancer will require long-term follow-up studies involving comparisons of breast cancer occurrence in patients with and without p53 mutations as well as functional assays to determine their significance.

Breast↗
PubMed2000

Correlation of p53 mutations in ThinPrep-processed fine needle breast aspirates with surgically resected breast cancers.

Mutations of the p53 gene are one of the most common genetic changes found in cancer; their presence may be prognostic and even influence treatment for breast cancer. In this study, we investigated whether DNA could be extracted from the residual cells left in ThinPrep-processed breast fine-needle aspirates and whether p53 gene changes could be detected in the DNA. The results were then correlated with DNA extracted from the matched formalin-fixed, paraffin-embedded, surgically resected breast cancer when available. DNA was successfully extracted from 54 of 62 aspirates and all 31 surgical specimens. p53 gene mutations were detected in 10 of the 54 cytology specimens (18.5%) and consisted of base pair substitutions or deletions. Silent or intronic p53 changes were found in five additional aspirates. One of the aspirates had two gene alterations, resulting in a total of six gene changes. Five of these changes were located in introns 6 or 9 and the sixth was a silent (no amino acid change) change in exon 6. p53 Polymorphisms were detected in nine aspirates (16.3%) and were located in codon 47 (one aspirate), codon 72 (six aspirates), and codon 213 (two aspirates). All cases with surgical material available showed identical p53 mutations, alterations, and polymorphisms in the resected tumors compared with those detected in the corresponding aspirates. The results of this study show that DNA suitable for analysis of p53 gene sequence changes can be successfully extracted from ThinPrep-processed breast fine-needle aspirates, and that identical alterations are detected in both the cytology and surgical specimens.

Adult↗
PubMed2000

Osteoid-producing tumors of bone.

Osteoid-producing skeletal tumors are commonly encountered lesions by radiologists. Lesions include both benign tumors--osteoma, enostosis, osteoid osteoma, and osteoblastoma--as well as the malignant neoplasm, osteosarcoma. Radiologic features of these lesions are emphasized in this article and are frequently diagnostic. In addition, clinical characteristics, treatment, and prognosis are reviewed.

Bone Neoplasms↗
PubMed1999

Paratesticular sarcoma: failure patterns after definitive local therapy.

PURPOSE: We examine disease control and patterns of failure for patients with adult paratesticular sarcoma treated with wide repeat excision and postoperative radiation for close margins. MATERIALS AND METHODS: A retrospective analysis was performed on 14 patients with paratesticular sarcomas referred to 1 institution from 1988 to 1995. RESULTS: Median followup was 50 months (range 26 to 90). Pathology review revealed malignant fibrous histiocytoma in 5 cases and liposarcoma in 3. Tumor grade was high in 8 cases. Microscopic residual disease was identified after repeat excision in 3 of 11 completely excised cases (27%). Cause specific survival 5 years after diagnosis was 70%. Both patients with local failure after wide excision had undergone initial intralesional excision and 1 had also received postoperative irradiation. In 5 patients metastases developed in the liver, lung, nodes or multiple sites 0 to 60 months after diagnosis. CONCLUSIONS: Simple excision is inadequate treatment for paratesticular sarcoma, since wide repeat excision revealed microscopic residual disease in 27% of completely excised cases. The 2 local failures occurred in patients with a history of inadvertent intralesional surgery, which may be a risk factor for local relapse after wide repeat excision. Adjuvant radiation should be considered for these patients as well as those with narrow repeat resection margins. Systemic failure was frequent in patients with high grade tumors, who will require effective systemic adjuvant therapy.

Adult↗
PubMed1999

Characterization of the mineral in calcified articular cartilagenous tissue formed in vitro.

Cartilagenous tissue with mineralized and nonmineralized layers was generated in vitro using bovine chondrocytes isolated from the deep zone of articular cartilage. Mineralization was induced by addition of either beta-glycerophosphate (beta-GP), phosphoethanolamine (PEA), or adenosine triphosphate (ATP). As this tissue might be suitable for use in joint resurfacing, the mineral of the calcified layer was characterized and compared to that present in the in vivo mineralized zone of bovine articular cartilage. Von Kossa staining demonstrated the presence of mineralization in the lower half of the tissue. The calcium content in the tissue varied from 4.9% to 7.8% of dry weight. Electron diffraction demonstrated a pattern consistent with hydroxyapatite. Brightfield transmission electron microscopy showed that the crystals were acicular and when measured under electron diffraction dark field imaging were 16.6 +/- 3.8 (beta-GP), 16.4 +/- 3.8 nm (ATP), and 17.0 +/- 6.3 nm (PEA) in length. The crystals were similar in size (16.0 +/- 5.5 nm) and appearance to the crystals in the in vivo calcified cartilage. This data suggests that the mineralization that occurs in vitro is similar to the in vivo cartilage.

Adenosine Triphosphate↗
PubMed1999

Deep zone articular chondrocytes in vitro express genes that show specific changes with mineralization.

We have developed a method to form reconstituted mineralized articular cartilagenous tissue in vitro from isolated deep zone chondrocytes. The aim of this study was to characterize further these cultures prior to and during mineralization. Histologic examination of the cells up to 8 days in culture showed that the chondrocytes had formed cartilagenous tissue. Similar to the in vivo cartilage, the chondrocytes expressed aggrecan, types II, I, and X collagens, osteopontin, and alkaline phosphatase (ALP). No osteocalcin mRNA expression was detected in either the in vivo cartilage or in vitro-generated tissue. Addition of beta-glycerophosphate (beta-GP) to the medium on day 5 induced mineralization and changes in gene expression. Expression of type X collagen, type II collagen, aggrecan core protein, and ALP were inhibited significantly between 2 h and 24 h after the addition of beta-GP. At 72 h, expression of these genes were still significantly depressed. These changes correlated with a decrease in collagen and proteoglycan synthesis, and ALP activity. Osteopontin expression increased within 8 h but returned to constitutive levels by 72 h. No change in type I collagen expression was detected. The changes in gene expression were not due to a direct effect of beta-GP itself, because similar gene changes occurred in the presence of phosphoethanolamine, another agent which induces mineralization. No changes in gene expression were seen in nonmineralizing cultures. In summary, articular chondrocytes grown on filter culture show expression of similar genes to the chondrocytes in the deep zone of articular cartilage and that changes in expression of specific genes were observed during tissue mineralization, suggesting that it is a suitable model to use to study the mechanism(s) regulating the localized mineralization of articular cartilage.

Aggrecans↗
PubMed1999

Treatment of giant-cell tumors of long bones with curettage and bone-grafting.

BACKGROUND: The use of curettage, phenol, and cement is accepted by most experts as the best treatment for giant-cell tumor of bone. The present study was performed to evaluate whether equivalent results could be obtained with curettage with use of a high-speed burr and reconstruction of the resulting defect with autogenous bone graft with or without allograft bone. METHODS: The prospectively collected records of patients who had a giant-cell tumor of a long bone were reviewed to determine the rate of local recurrence after treatment with curettage with use of a high-speed burr and reconstruction with autogenous bone graft with or without allograft bone. All of the patients were followed clinically and radiographically, and a biopsy was performed if there were any suspicious changes. RESULTS: Fifty-nine patients met the criteria for inclusion in the study. According to the grading system of Campanacci et al., two patients (3 percent) had a grade-I tumor, twenty-nine (49 percent) had a grade-II tumor, and twenty-eight (47 percent) had a grade-III tumor. Seventeen patients (29 percent) had a pathological fracture at the time of presentation. The mean duration of follow-up was eighty months (range, twenty-eight to 132 months). Seven patients (12 percent) had a local recurrence. Six of these seven were disease-free at the latest follow-up examination after at least one additional treatment with curettage or soft-tissue resection (one patient). One patient had resection and reconstruction with a prosthesis after a massive local recurrence and pulmonary metastases. CONCLUSIONS: Despite the high rates of recurrence reported in the literature after treatment of giant-cell tumor with curettage and bone-grafting, the results of the present study suggest that the risk of local recurrence after curettage with a high-speed burr and reconstruction with autogenous graft with or without allograft bone is similar to that observed after use of cement and other adjuvant treatment. It is likely that the adequacy of the removal of the tumor rather than the use of adjuvant modalities is what determines the risk of recurrence.

Adolescent↗
PubMed1999

Primary leiomyosarcoma of bone.

OBJECTIVE: This study describes radiographic and MR imaging features of primary leiomyosarcoma of bone. SUBJECTS AND METHODS: Twelve patients (five men and seven women, 39-79 years old) who were treated at two oncology centers for primary leiomyosarcoma of bone involving the femurs, tibia, ilium, and inferior pubic ramus were studied. None of the patients had preexisting disease or disease elsewhere at the time of diagnosis. Pathologic diagnosis was obtained in all patients. RESULTS: Radiographs of all patients showed a matrix that was exclusively osteolytic. In long bones (seven patients), the tumor had an average length of 11 cm (range, 7-17 cm) and revealed an elongated configuration. In the pelvis (five patients), the average length of the tumor was 10 cm (range, 4-15 cm). MR imaging confirmed an intramedullary lesion in all patients, with extension into the soft tissues in eight patients and no identifiable soft-tissue mass in the remaining four patients. Four of the five pelvic tumors had a prominent soft-tissue mass, whereas only four of the seven long bone lesions revealed a soft-tissue mass that was, in all instances, small. The tumor was hypointense on T1-weighted images and showed heterogeneous signal intensity on T2-weighted conventional and fast spin-echo sequences. We saw low signal intensity (short T2) in eight patients and homogeneous hyperintense signal intensity in one patient. In the remaining three patients, T2-weighted spin-echo sequences obtained with fat saturation showed high signal intensity (long T2) in the tumors. CONCLUSION: Primary leiomyosarcoma of bone is a rare tumor that on radiography reveals no matrix and on MR imaging reveals areas of T2 shortening in relation to fat on conventional and fast spin-echo sequences.

Adult↗
PubMed1998

Alveolar soft part sarcoma: review of nine cases including two cases with unusual histology.

AIM: Alveolar soft part sarcoma is a very rare tumour. Nine cases are reviewed in order to identify new aspects of this tumour. METHODS AND RESULTS: The clinical course, histological, immunohistochemical and ultrastructural features of nine cases of alveolar soft part sarcoma were reviewed. Proliferative activity and p53 protein accumulation were assessed immunohistochemically. The patients were aged between 18 and 70 years. In the cases with sufficient follow-up, survival was variable with two patients dying within 5 months and four alive at 4 years. Histologically all tumours had an alveolar component but one case also had a spindle component and another case had a pseudoglandular pattern. Six cases showed desmin immunoreactivity, one was muscle-specific actin positive, two were positive for S100 protein and three were positive for vimentin. MIB-1 immunostaining was seen in up to 35% of cells. Two cases showed p53 protein accumulation. CONCLUSIONS: There appeared to be no correlation between short term survival (4 years or less) and clinical presentation, adjuvant treatment, tumour size, histological grade, vascular invasion by tumour, proliferative index, or p53 protein accumulation. Although unusual, spindle cell or pseudoglandular components can be seen in alveolar soft part sarcoma.

Adult↗
PubMed1998

Cyclin D1 gene amplification and protein expression in benign breast disease and breast carcinoma.

Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.

Breast↗