Biomedical subjects

C G Kleer

Publications and source records attributed to C G Kleer.

13 recordsLinked to original sources

PubMed2004

Validation of a tissue microarray to study differential protein expression in inflammatory and non-inflammatory breast cancer.

AIMS: Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer with poor prognosis. The mechanisms responsible for the aggressive clinical evolution are incompletely understood. We constructed a tissue microarray (TMA) and validated its use in translational IBC research. Differential expression of proteins that might play a role in causing the IBC phenotype was studied. METHODS AND RESULTS: A TMA containing 34 IBC and 41 non-stage matched non-IBC tumours was constructed. Five core biopsies were taken for each IBC and three cores for each non-IBC tumour. The TMA was validated using three approaches: (1) the excellent concordance between immunohistochemical results of the initial pathological examination and the results obtained with the TMA for ER, PR and HER2/neu (kappa > 0.74); (2) the known differential expression between IBC and non-IBC for four bio-markers in IBC (ER, PR, p53 and HER2/neu) was confirmed ( p < 0.01); (3) the HER2/neu status using three different antibodies (CB11, TAB250 and HercepTest) was highly concordant (kappa > 0.75). Furthermore, the overexpression of E-Cadherin and RhoC GTPase in IBC ( p < 0.05) was confirmed. We did not find a differential expression pattern for carbonic anhydrase IX (CA IX) and EGFR. CONCLUSIONS: Using different approaches, we have validated the use of our TMA for studying differential protein expression in IBC and non-IBC. We confirm the overexpression of E-Cadherin and RhoC GTPase in IBC. The lack of differential expression for CA IX and EGFR might suggest the pathways are equally utilised in both types of breast cancer.

Adenocarcinoma↗

PubMed2001

Surgical pathology of Crohn's disease.

This article discusses the gross endoscopic and histologic features of Crohn's disease. Terms used to describe the pathologic features are defined, and possible mechanisms and implications of development are discussed. The gross endoscopic and histologic correlation and the roles of the pathologist and endoscopist in making the diagnosis of Crohn's disease are emphasized.

Biopsy↗

PubMed2001

Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast.

The histologic distinction between benign and malignant Phyllodes tumors (PT) is often difficult and arbitrary. We analyzed a group of benign and malignant PT to determine whether specific histologic features and expression of Ki-67 and p53 could be useful in distinguishing benign PT from malignant tumors. We also determined whether deletions in Chromosome 3p at the FHIT and hMLH1 loci are common abnormalities in PT. Twenty PT were histologically classified as benign (7) or malignant (13). Seven of the malignant PT were low grade, and six were high grade. Ki-67 and p53 immunohistochemistry was performed on all tumors and analyzed for the stromal and for the epithelial component. PCR-based loss of heterozygosity analyses were performed with the following markers on Chromosome 3p: D3S1478 (3p21.2--21.3), D3S1289 (3p21.1--21.2), and D3S1295 (3p14.3--21.1). The distribution of immunoreactivity for Ki-67 was analyzed by quantifying the percentage of positive nuclei and expressed as the labeling index (LI). Patients' ages ranged from 13 to 71 years (median: 51 y). After a mean follow-up period of 8 years, none of the PT metastasized, whereas three recurred locally. Although malignant PT were larger than benign PT (means, 7.1 versus 4.3 cm), this difference was not statistically significant. Five tumors had infiltrating margins, and 14 were circumscribed. The Ki-67 LI in low-grade malignant PT (16 +/- 25.5) was significantly higher than that in benign PT (3.6 +/- 4.8), whereas the LI in the high-grade malignant PT group (50 +/- 21.9) was significantly higher than that in low-grade malignant tumors (P =.012). The Ki-67 LI in the three tumors that recurred was less than 10%. Two of seven (29%) benign PT were focally positive for p53, whereas four of seven (57%) low-grade malignant and three of six (50%) high-grade malignant PT were diffusely positive for p53. The three tumors that recurred initially were histologically benign, as were two of the recurrences. One recurrent tumor evolved to a high-grade malignant PT. Margins were greater than 1 cm in all tumors except four, three of which recurred locally. No allelic loss of 3p was found. In summary, Ki-67 expression may assist in distinguishing benign from malignant PT in diagnostically difficult cases. 3p deletions do not play a significant role in the development of these tumors. Neither Ki-67 nor p53 can reliably predict recurrence. Histologically high-grade malignant PT have a favorable prognosis if widely excised. We emphasize the importance of adequate margins in the treatment of benign and malignant PT.

Breast Neoplasms↗

PubMed2001

Persistent E-cadherin expression in inflammatory breast cancer.

E-cadherin is a transmembrane glycoprotein that mediates epithelial cell-to-cell adhesion. Because loss of E-cadherin expression results in disruption of cellular clusters, it has been postulated that E-cadherin functions as a tumor suppressor protein. The role of E-cadherin in inflammatory breast cancer (IBC), a distinct and highly aggressive form of breast cancer, is largely unknown. The aim of our study was to elucidate whether E-cadherin expression contributes to the development and progression of the IBC phenotype and to investigate any differences in E-cadherin expression between IBC and stage-matched non-IBC. Forty-two breast cancer cases (20 IBC and 22 non-IBC) were identified. Strict and well-accepted criteria were used for the diagnosis of IBC. Clinical and pathologic features were studied, and formalin-fixed, paraffin-embedded tissue sections were immunostained for E-cadherin, estrogen and progesterone receptors (ER and PR, respectively), and HER2/neu. Statistical analysis was performed using Fisher's exact test. All IBC uniformly expressed E-cadherin, whereas 15 of the 22 (68%) of the non-IBC expressed the protein (P = .006). Intralymphatic tumor emboli in the IBC cases were also all E-cadherin positive. Two IBC tumors demonstrated invasive lobular histology, and both cases were positive for E-cadherin. Of the non-IBC cases, three were invasive lobular carcinomas, and all were positive for E-cadherin. No association was found between E-cadherin expression and ER, PR status, or HER2/neu overexpression. Our study demonstrates that there is a strong association between E-cadherin expression and IBC and suggests that E-cadherin may be involved in the pathogenesis of this form of advanced breast cancer. In our study, we demonstrate that circulating IBC tumor cells strongly express E-cadherin, thereby providing an important exception to the positive association between E-cadherin loss and poor prognosis in breast cancer.

Breast Neoplasms↗

PubMed2000

Molecular biology of breast cancer metastasis. Inflammatory breast cancer: clinical syndrome and molecular determinants.

Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer (LABC) that effects approximately 5% of women with breast cancer annually in the USA. It is a clinically and pathologically distinct form of LABC that is particularly fast growing, invasive, and angiogenic. Nearly all women have lymph node involvement at the time of diagnosis, and approximately 36% have gross distant metastases. Despite recent advances in multimodality treatments, the prognosis of patients with IBC is poor, with a median disease-free survival of less than 2.5 years. Recent work on the genetic determinants that underlie the IBC phenotype has led to the identification of genes that are involved in the development and progression of this disease. This work has been aided by the establishment of primary human cell lines and animal models. These advances suggest novel targets for future interventions in the diagnosis and treatment of IBC.

Animals↗

PubMed2000

Fine-needle aspiration of breast carcinomas with prominent lymphocytic infiltrate.

Carcinomas of the breast with prominent lymphoplasmacytic background are commonly encountered in cytology. The aim of this study was to assess the prevalence of different types of carcinomas that share this common feature, identify possible distinguishing cytologic features, and evaluate the diagnostic pitfalls in this group of tumors. Eighteen fine-needle aspirations (FNAs) of breast carcinomas with heavy lymphoplasmacytic background were reviewed. Histologic follow-up was reviewed in all cases. Of 18 cases, there were 9 invasive ductal carcinomas (IDC), and 9 medullary carcinomas (6 typical and 3 atypical). FNAs from typical medullary carcinomas (TMC) showed more severe nuclear atypia and macronucleoli than the cases of IDC and atypical medullary carcinomas (AMC). Gland formation was absent in the TMC but was common in IDC and AMC. No cytologic differences were noted between IDC and AMC. Nucleoli were larger in TMC (mean 4, microm) than in AMC (mean, 2 microm) and IDC (mean, 1.5 microm). We conclude that lymphocytes and plasma cells may be seen in different types of breast carcinomas and should not be considered a diagnostic feature of TMC. Features potentially helpful in the cytologic differential diagnosis of a carcinoma with prominent lymphoplasmacytic background are nucleolar size (4 microm in MC, vs. 1.5 and 2 microm in IDC and AMC, respectively) and the degree of nuclear atypia. Lymphocytosis may be part of the carcinoma or may originate from a lymph node involved by metastases. In rare cases, a prominent neutrophilic infiltrate may also be present.

Adult↗

PubMed2000

Squamous cell carcinoma of the thyroid: an aggressive tumor associated with tall cell variant of papillary thyroid carcinoma.

Squamous cell carcinoma of the thyroid (SCT) is an unusual neoplasm thought to arise as a primary tumor or as a component of an undifferentiated carcinoma. The role of p53 and Ki-67 as prognostic indicators in this type of tumor is not known. We studied eight cases of primary SCT. Three cases were analyzed for Ki-67 by immunohistochemistry and for p53 by immunohistochemistry and loss of heterozygosity. Seven patients were women, and one was a man (age range, 31 to 90 years). SCT were firm, were tan with areas of necrosis, and ranged in size from 2 to 8 cm. Histologically, they had islands of squamous cells with spindle cell areas (two of eight). In four of eight cases, SCT was associated with the tall cell variant of papillary carcinoma (TCV). Positive staining for p53 was seen in two of three cases, and in one of three the TCV was also positive for p53. Mean MIB1 labeling index was 30% and 17% in SCT and TCV, respectively. At the time of presentation, six of eight patients had cervical lymph node metastases. In one case, the primary tumor had SCT and TCV; however, only the SCT component metastasized. After mean follow-up of 48 months, one patient had died of disease, five were alive with recurrent or metastatic tumor, and two were lost to follow-up. Primary SCT is an aggressive neoplasm that may be found in association with TCV. p53 expression and high MIB1 labeling index occur in these tumors and may be useful prognosticators.

Adenocarcinoma, Papillary↗

PubMed1999

Endoscopic and histological patchiness in treated ulcerative colitis.

OBJECTIVE: Traditionally, contiguous distribution of inflammation (endoscopic and histological) with rectal involvement is thought to be important in distinguishing ulcerative colitis (UC) from Crohn's disease of the colon. Little long-term data are available that prove whether this rule holds during the course of disease as it is modified by time and treatment. The aim of this study was to investigate the prevalence of endoscopic and histological patchiness and rectal sparing in treated UC over time and to correlate these findings with treatment at the time of endoscopy. METHODS: Patients with well-established UC who underwent sequential colonoscopy or flexible sigmoidoscopy with biopsies were included in this study. Patients' medical records including endoscopy/biopsy reports and clinical status/symptoms/treatment at the time of endoscopy were reviewed retrospectively. RESULTS: A total of 32 patients (14 men, 18 women; median age, 45 yr; median UC duration, 15 yr) underwent 175 sequential endoscopies with biopsies (161 colonoscopies, 14 sigmoidoscopies; median, five endoscopies per patient; range, 3-10). Endoscopic and/or histological patchiness was present in 20 of 175 (11%) sequential endoscopies with biopsies over time from 12 of 32 (38%) patients. Endoscopic and/or histological rectal sparing was present in 27 of 175 (15%) of sequential endoscopies with biopsies over time from 14 of 32 (44%) patients. Seven patients had both patchiness and rectal sparing. Therefore, in 47 (27%) follow-up endoscopies in 19 (59%) patients, there was either patchy disease, rectal sparing, or both sometime during the course of disease with treatment. There was no significant difference in treatment, including steroid use and rectal therapy, between those with patchiness and/or rectal sparing and those without. CONCLUSIONS: Contrary to traditional teaching, endoscopic and histological patchiness of inflammation and rectal sparing are common during the course of disease in treated UC and seem to be unrelated to specific therapy.

Adolescent↗

PubMed1999

Relationship between mammographic screening intervals and size and histology of ductal carcinoma in situ.

OBJECTIVE: The objective of this study was to determine how the length of time between mammographic screenings is related to the size, grade, and histology of mammographically detected ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: We retrospectively reviewed 166 consecutive mammograms of women evaluated for DCIS with (n = 24) and without (n = 142) microinvasion. The size of the DCIS was determined by the maximum diameter as measured on the mammogram. After pathologic analysis, DCIS was classified by histologic architecture, nuclear grade, presence of microinvasion, and presence of multifocality. Four screening intervals were defined: annual (6-17 months), biennial (18-29 months), triennial (> or = 30 months), and first time. Patients were grouped according to screening intervals. The average age of all groups was 55 years. RESULTS: The annual group (mean size of DCIS, 1.69 cm) had significantly smaller DCIS than did the biennial (mean size, 2.27 cm), triennial (mean size, 3.49 cm), or first time groups (mean size, 3.29 cm) (p = .003). Comedo histology was more frequently observed in patients screened biennially (73.7%) than in those screened annually (46.8%) (p = .05). High-grade nuclear histology was more commonly seen in the biennial (76.3%) than in the annual (48.1%) screening group (p = .008). We found no significant correlation between screening interval and the incidence of microinvasion and multifocality. CONCLUSION: Small, low-grade noncomedo DCIS was more common in the annual mammographic screening group than in the biennial screening group. A direct relationship was found between DCIS size and length of screening interval: DCIS detected at annual screening was smaller than that found at biennial screening, which in turn was smaller than DCIS revealed at triennial screening. This study provides inferential support for annual screening mammography for DCIS detection and management.

Breast↗

PubMed1998

Adenoid cystic carcinoma of the breast: value of histologic grading and proliferative activity.

Adenoid cystic carcinoma of the breast is an uncommon carcinoma with a distinctive histology. Prognosis is favorable, although recurrence and distant metastases have been described. We assessed whether histologic features and proliferative activity can identify aggressive neoplasms. We studied 31 cases of adenoid cystic carcinoma (age range of patients, 33 to 74 years). Three histologic grades were defined: grade I: completely glandular; grade II: < 30% solid areas, and grade III: > or = 30% solid pattern. In 19 of 31 cases, immunohistochemical stains for estrogen receptor were available. Twelve of 31 cases were immunohistochemically stained for Ki-67 antigen using MIB1 antibody. Ten of 20 tumors were subareolar. All tumors were grossly circumscribed; however, 12 of 20 (60%) had focal infiltration peripherally. Five of 19 tumors were estrogen receptor positive. There was no statistical correlation between MIB1 score and histologic grade, nuclear grade, infiltration of the adjacent fat or breast parenchyma, or estrogen receptor status. All patients were alive with no evidence of disease after a median follow-up of 7 years. Neither histologic or nuclear grading nor proliferative activity were useful prognosticators. None of the tumors had lymph node metastases. Therefore, axillary lymph node dissection may not be necessary. Because more than half of adenoid cystic carcinomas are infiltrative focally, the most important therapeutic goal is complete tumor removal with uninvolved margins of excision.

Adult↗

PubMed1998

Ulcerative colitis: patterns of involvement in colorectal biopsies and changes with time.

Chronic inflammation, both endoscopic and histologic, in a contiguous and symmetric distribution is said to be important in distinguishing ulcerative colitis (UC) from Crohn's disease. Little is known whether this rule holds during the course of the disease and whether endoscopic/histologic correlation persists. In this study, we analyzed histologic patterns of UC in sequential sets of biopsy specimens to assess whether endoscopic and histologic findings correlate with time and treatment and to see whether distribution changes. Two hundred seventeen sets of colorectal biopsy specimens from 797 sites from 41 patients with clinical UC were studied and correlated with endoscopic findings. Each biopsy specimen was classified as definite or suspicious for chronic colitis or normal. Two histologic patterns of disease were identified: (1) diffuse, when all areas in all pieces from a biopsy segment had clear-cut colitis and (2) nondiffuse, when not all pieces were involved or single pieces had disease and normal mucosa both. Of 41 patients, the maximal extent of histologic disease was pancolitis in 30; 25 had less extensive disease at some point in the course. The maximal extent was left-sided in eight patients, seven of whom had less extent at some point. Of the three patients in whom the maximal extent was proctosigmoiditis, in one the inflammation disappeared. Seventy percent of the biopsy sites had diffuse patterns and 30% had nondiffuse. Histologic and endoscopic disease reverted to normal in 22 and 24 of 41 patients, respectively. Endoscopic and histologic findings were similar in 65% of the biopsy sites. Our results indicate that in long-standing UC (1) histologic disease may revert to normal mucosa, (2) because endoscopy alone may be insufficient to identify the mucosa as normal, biopsies should also be performed on the endoscopically normal mucosa, (3) the full extent of UC often is not established by a single set of biopsies, and (4) nondiffuse chronic inflammation and rectal sparing occurs in UC and are not necessarily markers of Crohn's disease.

Adolescent↗

PubMed1997

Autologous blood donation prior to anatomical radical retropubic prostatectomy: is it necessary?

OBJECTIVES: To determine if autologous blood donation prior to anatomical radical retropubic prostatectomy, given current improvements in surgical technique, is necessary. METHODS: The medical records of 200 consecutive patients undergoing radical retropubic prostatectomy for clinically localized prostate cancer were reviewed with regard to (1) preoperative hematocrit (HCT); (2) estimated blood loss (EBL); (3) postoperative HCT prior to discharge; (4) number of units of autologous blood donated; and (5) number of units of autologous and homologous blood transfused. In addition, the charges associated with autologous blood donation were determined via telephone interview with 14 blood donation centers across the United States. RESULTS: Overall, 189 patients (95%) did not require a homologous blood transfusion. Sixty-four patients (32%) donated autologous units and 136 patients (68%) did not. Of the patients who had donated, only 17 (27%) received their blood back, and none (0%) received any homologous blood. Eleven (8%) of the 136 nondonors received a blood transfusion. The autologous donors, in comparison with nondonors, were found to have a significantly lower preoperative HCT (mean +/- standard deviation: 40 +/- 4.0% versus 42 +/- 2.9%, P < 0.05). However, there was no statistically significant difference in the mean EBL between the two groups, autologous donors versus nondonors (771 +/- 370 versus 737 +/- 425 cc, P = 0.23). The autologous donors had a smaller mean change in HCT versus the nondonors (-9.3 +/- 5.1% versus -11.2 +/- 4.4%, P < 0.05), reflecting an increased willingness to transfuse patients who have autologous units available. With regard to cost, patients, on average, can expect to be charged as much as $745 per unit of autologous blood donated. CONCLUSIONS: These findings suggest that preoperative blood donation prior to radical prostatectomy may not be necessary, because 95% of the patients did not require a homologous blood transfusion. In addition, autologous blood donation can be associated with substantial costs in both time and money. Thus, autologous donation should be left as an option for the patient and should not be considered routine practice.

Adult↗

PubMed1996

Epithelioid hemangioendothelioma of bone.

Epithelioid hemangioendothelioma of bone is a rare tumor of vascular origin. A series of 40 cases from the Mayo Clinic files was studied to define the pathologic features of this disease and to evaluate any histologic or clinical factor influencing outcome. More than 50% of the tumors were multicentric, with a predilection for bones of a particular anatomical area. In this series, patients with multifocal tumors did not have a better prognosis than those with unicentric disease. We could not predict the outcome of cases on the basis of the histologic features. Visceral involvement was the most important criterion in predicting prognosis. Resection is still the primary treatment for these tumors. Radiotherapy may be useful for surgically inaccessible tumors. Too few patients have received adjuvant chemotherapy to evaluate its usefulness in this setting.

Adolescent↗