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L R Bégin

Publications and source records attributed to L R Bégin.

At least 19 recordsLinked to original sources
PubMed2005

Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study.

Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB-p52 and RelA-RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.

Adenocarcinoma↗
PubMed2005

Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment.

BACKGROUND: Elevated levels of the cell cycle protein cyclin E, and low levels of its inhibitor, p27(Kip1), have been associated with a poor prognosis following breast cancer. Some studies have found that germline mutations in the breast cancer susceptibility gene, BRCA1, are also associated with an inferior survival rate. The relationship between cyclin E/p27(Kip1) levels, BRCA1 status and outcome has not been studied in detail. PATIENTS AND METHODS: We analyzed a historical cohort of 288 Ashkenazi Jewish women who were diagnosed with breast cancer between 1980 and 1995 and were previously tested for BRCA1/2 mutations. Protein levels of cyclin E and p27(Kip1) were assessed by immunohistochemistry. Breast cancer-specific survival (BCSS) was the main outcome measured. RESULTS: The median follow-up was 8 years. Thirty tumors carried germline BRCA1 mutations. These tumors were more likely to have high cyclin E protein levels [odds ratio (OR) 9.5; P <0.001] and low p27(Kip1) protein levels (OR 2.8; P=0.03) than tumors from patients without BRCA1/2 mutations. High cyclin E expression level was the strongest predictor of BRCA1 germline mutations (multivariate OR 4.7; P=0.004). On univariate analysis, high cyclin E protein levels [relative risk (RR) 2.6; P <0.001] and low p27(Kip1) protein levels (RR 2.3; P=0.006) were significant prognostic factors for a poorer BCSS. In Cox multivariate models, high cyclin E levels remained an independent indicator of poor outcome only in the subgroup of patients who did not receive chemotherapy (P=0.002). CONCLUSIONS: In this ethnically restricted cohort, a high level of cyclin E is a characteristic of BRCA1-related breast cancer, and is a marker of poor prognosis following breast cancer, particularly in the absence of adjuvant chemotherapy.

Adult↗
PubMed2004

Comparative evaluation of various prostate specific antigen ratios for the early detection of prostate cancer.

OBJECTIVE: To compare the performance of various ratios using total prostate specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early detection of prostate cancer. PATIENTS AND METHODS: The study included 535 consecutive patients evaluated at a prostate cancer detection clinic between January 1998 and October 1999. Patients had blood samples drawn before transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA. Receiver operating characteristic (ROC) curves (sensitivity vs 1 - specificity) were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA, tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC) were calculated for each ratio. The performance of each ratio over all patients or in those with a tPSA of 4-6 or 4-10 ng/mL were evaluated. RESULTS: Of the 535 patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone. Furthermore, in patients with a tPSA of 4-10 ng/mL, tPSA/PV (0.72), cPSA/PV (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better than tPSA alone (0.52). Finally, in patients with a tPSA of 4-6 ng/mL, PSA/PV and cPSA/PV performed better than the other ratios. CONCLUSIONS: The use of PSA ratios gives a higher sensitivity and specificity for detecting prostate cancer than the use of tPSA alone.

Early Diagnosis↗
PubMed2003

Glomeruloid microvascular proliferation is associated with p53 expression, germline BRCA1 mutations and an adverse outcome following breast cancer.

Glomeruloid microvascular proliferation (GMP) in breast cancer independently adversely affected survival (relative risk 1.9, 95% CI: 1.2-3.0), particularly among women who received adjuvant chemotherapy (10-year survival 27 vs 69%, P=0.0003), and was significantly associated with p53 overexpression and BRCA1 germline mutations. The presence of GMP may influence treatment decisions.

Adult↗
PubMed2003

Serum insulin-like growth factor (IGF)-1 and IGF-binding protein-3 do not correlate with Gleason score or quantity of prostate cancer in biopsy samples.

OBJECTIVE: To examine the relationship of serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3) with histological cancer characteristics in men undergoing transrectal ultrasonography (TRUS)-guided biopsy. PATIENTS AND METHODS: Patients (652), with either an elevated serum prostate-specific antigen level or an abnormal digital rectal examination, were initially evaluated by TRUS and sextant prostatic needle biopsy. Blood was drawn before biopsy, serum extracted and stored frozen until IGF-1 and IGFBP-3 were measured. In all, 241 patients had prostate cancer (37%) and were included in this study. The number of positive biopsies, the volume of tumour in each positive biopsy and the Gleason score were recorded. RESULTS: Of the 241 patients, 37 had five or six positive biopsies (from six), 128 had two to four and 76 had one. Serum IGF-1 did not correlate with the number of positive biopsies, with means of 176.7, 178.3 and 164.4 ng/mL, respectively (P = 0.3), while the mean IGFBP-3 was 2695, 2795 and 2572 ng/mL, respectively (P = 0.09). The additive percentiles of tumour volume in positive biopsies were assessed for each patient but serum IGF-1 and IGFBP-3 did not correlate (P = 0.7 and 0.9, respectively). In all, 92 patients had a Gleason score of < 7, 80 a score of 7 and 69 a score of > 7; the mean (sd) IGF-1 levels for the three groups were 181 (39), 174.6 (35) and 176 (26) ng/mL, and the mean IGFBP-3 2798 (240), 2735 (284) and 2647 (221) ng/mL, respectively, none of the differences being statistically significant. CONCLUSIONS: Serum IGF-1 and IGFBP-3 do not correlate with quantity of cancer or Gleason score in biopsy samples from patients with prostate cancer.

Aged↗
PubMed2002

Vascular endothelial growth factor and signaling in the prostate: more than angiogenesis.

In cloning tyrosine kinase genes in dog prostate cells, a fragment of the vascular endothelial growth factor (VEGF) receptor 1 or Flt-1 was sequenced. To test for a functional protein, Flt-1 antibodies were used to probe immunoprecipitated tyrosine phosphorylated proteins. Western blotting revealed a major 170-180 kDa band and a few bands below 116 kDa in dog prostate and human prostatic carcinoma PC-3 cells, with higher levels in PC-3. Similar results were obtained with human placental membranes used as a source of Flt-1. That the major Flt-1 tyrosine phosphorylated protein was likely VEGF-R1 and part of VEGF signaling pathways was shown by enhanced level of only this protein when PC-3 cells were exposed to VEGF. Accordingly specific cell surface receptor complexes, displaced by VEGF but not EGF and compatible with Flt-1 in size, were revealed by chemical cross-linking after 125I-VEGF binding. Similarly to the prostatic neuroproduct, gastrin-releasing peptide/bombesin, VEGF directly triggered the tyrosine phosphorylation of focal adhesion kinase and stimulated PC-3 cell motility. The titration of prostate tissue sections with VEGF-A antibodies revealed a confined staining in chromogranin A and/or serotonin positive neuroendocrine (NE) cells, including in primary tumors and lymph node metastases. Given that NE differentiation is associated with advanced disease, that NE cells are a significant source of VEGF in prostatic tumors, and that VEGF directly act on prostate cancer cells in vitro, VEGF-A may be more than angiogenic in prostate cancer and hence favor progression by affecting tumor cells.

Amino Acid Sequence↗
PubMed2002

Comparative evaluation of total PSA, free/total PSA, and complexed PSA in prostate cancer detection.

OBJECTIVES: To compare the performance of prostate-specific antigen (PSA), the free/total PSA (F/T PSA) ratio, and complexed PSA (cPSA) in prostate cancer detection. METHODS: Five hundred thirty-five patients evaluated at the UROMED prostate cancer detection clinic had total PSA, free PSA, and cPSA measured before undergoing transrectal ultrasonography and sextant prostate biopsies. A direct comparison was performed between the different PSA assays to evaluate their ability to detect prostate cancer. RESULTS: Of the 535 patients evaluated, 38.1% had prostate cancer detected. The mean age of the entire population was 63.6 years (range 35 to 86). Abnormal digital rectal examination findings were present in 33.4% of the patients. The mean and median values of PSA and cPSA were significantly higher and the F/T PSA ratio was lower in patients with prostate cancer. The F/T PSA ratio performed better than either cPSA or total PSA. A higher specificity was observed with the F/T PSA ratio than with cPSA using either the entire patient population or subsets of patients with PSA levels between 4.0 and 10 ng/mL or 4.0 to 6.0 ng/mL. CONCLUSIONS: The use of the F/T PSA ratio offers improved prostate cancer detection compared with either cPSA or total PSA.

Adult↗
PubMed2001

Diffuse hepatic intravascular carcinomatous embolization resulting in fatal liver failure: a clinicopathologic study of 4 cases.

The authors report four cases in which patients died of acute or fulminant hepatic failure resulting from massive intravascular metastatic carcinomatous embolization, a rarely reported manifestation of metastatic disease. Neoplasms were high grade carcinomas. Tumor emboli were present within portal branches ranging 0.12-2.9 mm in diameter and were free floating or attached to the vascular wall, with or without varying degrees of superimposed organization. In one case, intravascular tumor necrosis was prominent and appeared as granular casts with superimposed dystrophic calcification and/or entrapped foamy histiocytes. There were associated geographical areas of parenchymal (4 cases) and tumor (1 case) ischemic necrosis with a multifocal and regional topographic distribution. An associated predominant pattern of intrasinusoidal tumor infiltration (with or without fibrosis) was present in 3 cases, whereas the fourth case had underlying micronodular cirrhosis, providing ancillary evidence for preexisting altered intrahepatic microcirculation. The literature on fatal hepatic failure resulting from neoplasia is reviewed with a reassessment of its pathobiological significance.

Acute Disease↗
PubMed2001

The dramatic presentation of colonic lipomata: report of two cases and review of the literature.

Colonic lipoma with a dramatic presentation requiring urgent operation is a rare occurrence. We report two such cases in conjunction with a review of the literature on colonic lipomata. Clinicopathologic features of two patients who required urgent resection were studied. The preoperative diagnosis of colonic lipoma was suggested on imaging study in one case. A MEDLINE search was conducted with a special goal of revealing cases with a dramatic presentation. One patient presented with rectal bleeding and intussusception related to a partially infarcted 4.5-cm submucosal lipoma of the lower descending colon. The second patient presented with intestinal obstruction related to a near-totally infarcted 6-cm submucosal lipoma at the splenic flexure. In both cases a florid reactive vascular and fibro-/myofibroblastic proliferation and associated hyperplastic mucosal pattern were present at the base and edge of the lipoma. Among 275 previously reported cases of colonic lipoma 28 patients had a dramatic presentation with pain and/or rectal bleeding being the most significant prodromal symptom. In this subset the lipomas tended to be larger, frequently had associated marked necrosis/ulceration, and were less likely to be located in the ascending colon/cecum. Whereas colonic lipomas are relatively common occasional cases present dramatically with massive bleeding, intussusception, or even perforation for which emergency operation is required. Such lipomas usually reveal marked ischemic changes.

Adult↗
PubMed2000

Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer.

PURPOSE: Decreased levels of the cyclin-dependent kinase inhibitor p27(Kip1) in breast cancer are associated with a poor outcome. The prognostic significance of BRCA1/2 mutations is less clear, and the relationship between BRCA1/2 mutation status, p27(Kip1) protein levels, and outcome has not been studied. PATIENTS AND METHODS: Pathology blocks from 202 consecutive Ashkenazi Jewish women with primary invasive breast cancer were studied. Tumor DNA was tested for the three common BRCA1/2 founder mutations present in Ashkenazi Jews, and p27(Kip1) expression was evaluated by immunohistochemistry. The median follow-up was 6.4 years. RESULTS: Thirty-two tumors (16%) were positive for a BRCA1/2 mutation. Low p27(Kip1) expression was seen in 110 tumors (63%) and was significantly associated with BRCA1/2 mutations (odds ratio, 4.0; 95% confidence interval [CI], 1.4 to 11.1; P =.009). BRCA1/2 mutation carriers had a significantly worse 5-year distant disease-free survival (DDFS) compared with women without BRCA1/2 mutations (58% v 82%; P =.003). Similar results were seen for women whose tumors expressed low levels of p27(Kip1), compared with those with high levels (5-year DDFS, 68% v 93%; P<.0001). In a multivariate analysis, both BRCA1/2 mutation and low p27(Kip1) expression were associated with a shorter DDFS (relative risk [RR], 2.1; 95% CI, 1.0 to 4.3; P =.05; and RR, 3.9; 95% CI, 1.4 to 11.1; P =.01, respectively). CONCLUSION: In this study, we showed that BRCA1/2 mutations were associated with low levels of p27(Kip1) in breast cancer. Both BRCA1/2 and p27(Kip1) status were identified as independent prognostic factors.

Adult↗
PubMed2000

Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome.

BACKGROUND: The association between BRCA1 germ-line mutations and breast cancer prognosis is controversial. A historical cohort study was designed to determine the prognosis for women with axillary lymph node negative hereditary breast cancer. PATIENTS AND METHODS: We tested pathology blocks from 118 Ashkenazi Jewish women with axillary lymph node negative breast cancer for the presence of the two common BRCA1 founder mutations, 185delAG and 5382insC. Patients were followed up for a median of 76 months. Somatic TP53 mutations were screened for by immunohistochemistry, and direct sequencing was performed in the BRCA1-positive tumours. RESULTS: Sixteen breast cancer blocks (13.6%) carried a BRCA1 mutation. Young age of onset, high nuclear grade, negative estrogen receptor status and over-expression of p53 were highly associated with BRCA1-positive status (P-values all <0.01). BRCA1 mutation carriers had a higher mortality than non-carriers (five-year overall survival, 50% and 89.6%, respectively, P = 0.0001). Young age of onset, estrogen receptor negative status, nuclear grade 3, and over-expression of p53 also predicted a poor outcome. Cox multivariate analyses showed that only germ-line BRCA1 mutation status was an independent prognostic factor for overall survival (P = 0.01). Among nuclear grade 3 tumours, the BRCA1 mutation carrier status was a significant prognostic factor of death (risk ratio 5.8, 95% confidence interval: 1.5-22, P = 0.009). Sequencing of BRCA1-related breast cancers revealed one TP53 missense mutation not previously reported in breast cancer. CONCLUSIONS: Using a historical cohort approach, we have identified BRCA1 mutation status as an independent prognostic factor for node negative breast cancer among the Ashkenazi Jewish women. Those managing women carrying a BRCA1 mutation may need take these findings into consideration. Additionally, our preliminary results, taken together with the work of others suggest a different carcinogenic pathway in BRCA1-related breast cancer, compared to non-hereditary cases.

Adult↗
PubMed1999

Searching for an intrinsic neuroendocrine cell in the kidney. An immunohistochemical study of the fetal, infantile and adult kidney.

The pathogenesis of primary renal carcinoid tumor is unknown. One hypothesis has implied derivation from a yet unrecognized intrinsic neuroendocrine cell in the renal parenchyma/hilum either as a minute endocrineparacrine constituent or resulting from entrapped/misplaced progenitor cells of the so-called dispersed neuroendocrine system during organogenesis. Immunohistochemical staining for chromogranin and serotonin was systematically performed on a whole-mount and geographically mapped normal adult kidney, kidneys from 15 fetuses (age range: 15 to 38 weeks), and renal specimens from 18 infants/children (age range: 7 days to 123 months). Minute paraganglion nests (composed of chromogranin positive/serotonin negative chief cells and S-100 protein positive dendritic cells) were incidentally detected within the renal hilum primitive stroma (unilaterally) of two fetuses at 22 and 26 weeks. Sequestration and persistence of such paraganglion nests during renal growth and maturation would offer a basis for the rare occurrence of extra-adrenal paraganglioma involving the renal hilum/pedicle. Otherwise, no neuroendocrine cell was detected within the renal parenchyma or hilum, therefore not validating/sustaining the aforementioned hypothesis in the pathogenesis of renal carcinoid tumor.

Carcinoid Tumor↗
PubMed1999

Fibromatosis.

Fibromatosis represents a diverse group of fibroproliferative tumours. Their behaviour and pathological qualities are situated in an intermediate position between benign and malignant disease. The following represents the pathological and radiological presentation of a 29-year-old female with fibromatosis.

Adult↗
PubMed1999

The effect of the I1307K APC polymorphism on the clinicopathological features and natural history of breast cancer.

The I1307K polymorphism in APC has been found to predispose to colorectal cancer in Ashkenazi Jews, and has recently been associated with an increased risk for breast cancer in the same population. In that study, we genotyped 205 paraffin-embedded breast cancers from Ashkenazi Jewish women diagnosed below the age of 65. We now present an extended analysis, with clinicopathological correlations between carriers of I1307K and non-carriers. Twenty-four of 209 cases (11.5%, 95% confidence interval 7.5-16.6) were found to carry the I1307K polymorphism. When stratifying the data by other relevant clinicopathological variables, we observed no association between the presence of this polymorphism and age at diagnosis (P = 0.52), grade (P = 0.074), tumour size (P = 0.99), lymph node status (P = 0.82), oestrogen receptor status (P = 0.23) or P53 immunoreactivity (P = 0.80). The breast-cancer specific 5-year survival for women with I1307 K polymorphism was 88.9% compared with 81.6% in women without I1307K (P = 0.34). Using microdissected samples and direct sequencing, no somatic mutations were observed in any of the 24 I1307K-positive cases. Single-strand conformation analysis of 158 of the I1307K-negative breast cancers that were available for study revealed no mobility shifts. We conclude that the presence of the I1307K polymorphism does not appear to be associated with any particular clinicopathological feature of breast cancer and importantly, does not affect the prognosis.

Adenomatous Polyposis Coli Protein↗
PubMed1998

Priapism secondary to penile metastasis: a report of two cases and a review of the literature.

Malignancy metastasis to the penis is an uncommon clinicopathological entity. We present two cases of malignant priapism following penile metastasis, in which the diagnosis was established by core needle biopsy of the corpus cavernosum. Primary tumors were urothelial carcinoma of the urinary bladder in one case (the patient having concomitant high-grade prostatic adenocarcinoma) and prostatic adenocarcinoma in the other. The clinicopathological features of 51 previously reported cases of penile metastasis in the recent literature are reviewed.

Adenocarcinoma↗