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D Grignon

Publications and source records attributed to D Grignon.

At least 19 recordsLinked to original sources
PubMed2000

Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential.

The involvement of 12-lipoxygenase (12-LOX) expression and function in tumor metastasis has been demonstrated in several murine tumor cell lines. In addition, 12-LOX expression was detected in human prostatic tumors and correlated to the clinical stage of disease. Here we provide data that human prostate cancer cell lines express the platelet-type isoform of 12-LOX at both the mRNA and protein levels, and immunohistochemistry revealed 12-LOX expression in human prostate tumors. The enzyme was localized to the plasma membrane, cytoplasmic organelles and nucleus in non-metastatic cells (PC-3 nm) and to the cytoskeleton and nucleus in metastatic cells (DU-145). After orthotopic/intraprostatic injection of tumor cells into SCID mice, the metastatic prostate carcinoma cells (DU-145) expressed 12-LOX at a significantly higher level compared with the non-metastatic counterparts, PC-3nm. The functional involvement of 12-LOX in the metastatic process was demonstrated when DU-145 cells were pretreated in vitro with the 12-LOX inhibitors N-benzyl-N-hydroxy-5-phenylpentamide (BHPP) or baicalein, the use of which significantly inhibited lung colonization. These data suggest a potential involvement of 12-LOX in the progression of human prostate cancer.

Animals↗
PubMed2000

Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials.

PURPOSE: To assess the impact of short-term and long-term androgen suppression on the disease-specific and overall survival of 2200 men treated with radiotherapy on one of 5 prospective randomized trials when stratified by prognostic risk groups. METHODS AND MATERIALS: Between 1975 and 1992, 2742 men were treated for clinically localized prostate cancer on one of 5 consecutive prospective Phase III randomized trials. Patients were selected for this analysis if they were deemed evaluable and eligible for the trial, and if follow-up information was available. For this analysis patients were stratified into four previously described prognostic risk groups: Group 1 patients had a Gleason score (GS) = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The median pretreatment prostate-specific antigen (PSA) was 25 ng/ml for the 434 evaluable patients for whom this information was available. The median follow-up times for patients treated on early studies exceeded 11 years, and for more recent studies 6 years. RESULTS: Risk group 2 patients with "bulky" or T3 disease appeared to have a disease-specific survival benefit at 8 years with the addition of 4 months of goserelin and flutamide. Group 3 and 4 patients were noted to have an approximately 20% higher survival at 8 years with the addition of long-term hormonal therapy (p < or =0.0004). CONCLUSIONS: Based on this meta-analysis of RTOG trials, subsets of patients can be identified who either do not appear to benefit from the use of hormonal therapy, benefit from short-term hormonal therapy, or who benefit only from long-term hormonal therapy. These observations should be confirmed by prospective randomized trials before they can be considered conclusive. In the meantime, however, these observations provide rational guidelines for deciding who should receive hormonal therapy and for how long.

Androgen Antagonists↗
PubMed2000

Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials.

PURPOSE: Gleason score (GS), T stage, and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy (XRT). In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival (DSS) death from prostate cancer. METHODS AND MATERIALS: Men entered on one of four Radiation Therapy Oncology Group (RTOG) Phase III randomized trials between 1975 and 1992, for clinically localized prostate cancer (CAP) (n = 1557), were selected for this analysis. Patients were included if: 1) they were evaluable, and eligible for the trial; 2) they received no hormonal therapy with their initial treatment; and 3) follow-up was available. For this study a DSS event was declared if: 1) death was certified as due to CAP; 2) death was due to complications of treatment; or 3) death was from unknown causes with active malignancy. The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively. Subgroups were identified based on their pretreatment GS, T-stage, and lymph node such that patients with similar risk of dying from prostate cancer were combined. RESULTS: By combining patients with similar DSS, four subgroups were identified. Risk Group 1 patients had a GS = 2-6, and T1-2Nx; Group 2: GS = 2-6, T3Nx; or GS = 2-6, N+, or GS = 7, T1-2Nx; Group 3: T3Nx, GS = 7; or N+, GS = 7, or T1-2Nx, GS = 8-10; and Group 4 patients were T3Nx, GS = 8-10, or N+, GS = 8-10. The 5-, 10-, and 15-year DSS was 96%, 86%, and 72%; 94%, 75%, and 61%; 83%, 62%, and 39%; and 64%, 34%, and 27% for Groups 1 through 4, respectively. CONCLUSIONS: Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.

Aged↗
PubMed2000

Prostate cancer biochemical recurrence stage for stage is more frequent among African-American than white men with locally advanced but not organ-confined disease.

OBJECTIVES: To determine whether outcome differences between African-American men (AAM) and white men with prostate cancer (PCa) will still be present if we control for stage in a large cohort of men. It is well established that AAM have a worse outcome from PCa than white men. METHODS: We examined 848 consecutive patients who underwent radical prostatectomy at Wayne State University, Karmanos Cancer Institute, between 1991 and 1995. The mean follow-up was 34 months (range 1.5 to 75). We included men with Gleason score 7 (4 + 3) with those men with Gleason score 8 to 10 for racial/ethnic comparisons. RESULTS: AAM and white men diagnosed with organ-confined PCa demonstrated similar prostate-specific antigen (PSA) levels, Gleason grade, and biochemical recurrence. However, AAM diagnosed with non-organ-confined disease demonstrated higher PSA levels and a higher incidence of recurrence than did white men with non-organ-confined disease. There was a trend toward AAM having a greater proportion of high-grade lesions than white men when PCa was not organ confined. The evidence suggests that the difference in recurrence among AAM versus white men is based on pretreatment PSA, grade, extracapsular extension, and positive surgical margins. Seminal vesicle invasion predicted a worse prognosis equally for both AAM and white men. CONCLUSIONS: A difference in biochemical recurrence was not detected between AAM and white men with organ-confined PCa after radical prostatectomy. PSA was higher in AAM than in white men with pathologically locally advanced PCa, and the biochemical recurrence was greater. AAM had a greater percentage of high Gleason grade lesions compared with white men, and this difference approached statistical significance. We hypothesize that AAM have a more rapid growth rate of PCa, which may be responsible for these clinical findings. Further investigations of the biology of PCa are needed to understand these findings.

Black or African American↗
PubMed2000

Survival advantage from higher-dose radiation therapy for clinically localized prostate cancer treated on the Radiation Therapy Oncology Group trials.

PURPOSE: We evaluated the effect of external-beam radiation therapy on disease-specific survival (death from causes related to prostate cancer) and overall survival in men with clinically localized prostate cancer. METHODS: From 1975 to 1992, 1,465 men with clinically localized prostate cancer received radiation therapy on four Radiation Therapy Oncology Group phase III randomized trials and were pooled for this analysis. No one received androgen-deprivation therapy with his initial treatment. All original histology had central pathologic review for grading using the Gleason classification system. Total delivered radiation dose ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years. RESULTS: A Cox regression model revealed that Gleason score was an independent predictor of disease-specific survival and overall survival. The 10-year disease-specific survival rates by Gleason score were as follows: score of 2 through 5, 85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%. Stratifying outcome by this important prognostic factor revealed that higher radiation dose was a significant predictor for improved disease-specific survival and overall survival only for those patients whose cancers had Gleason scores of 8 through 10 (P <.05). After adjusting for clinical T stage, nodal status, and age, treating with a higher radiation dose was associated with a 29% lower relative risk of death from prostate cancer and 27% reduced mortality rate (P <.05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.

Aged↗
PubMed2000

Should the age specific prostate specific antigen cutoff for prostate biopsy be higher for black than for white men older than 50 years?

PURPOSE: Investigators who have examined age specific reference ranges recommend a higher prostate specific antigen (PSA) cutoff for biopsy for black than for white men older than 50 years. We controlled for PSA to determine whether age specific reference range cutoffs for diagnosis defined by the Walter Reed Army Medical Center group (Walter Reed group) would improve the disproportionate prostate cancer prognosis between black and white men. MATERIALS AND METHODS: We studied 651 consecutive patients who underwent radical prostatectomy at Wayne State University between 1991 and 1995 with a mean followup of 34 months (range 1.5 to 75). Log rank tests were used to determine the homogeneity of survival functions between black and white men with similar PSA ranges, and between groups defined by age specific PSA reference ranges for each race. RESULTS: Disease stage and grade were similar or worse in black men for any PSA range, and biochemical disease-free survival was similar or worse within each range. Black men had a higher percentage of high grade prostate cancer than white men 60 to 69 years old who would not have undergone biopsy using the Walter Reed group proposed PSA cutoff. CONCLUSIONS: Black men have similar or worse prostate cancer severity and outcome than white men with similar PSA ranges. Using age specific reference ranges for the PSA test defined by the Walter Reed group, black men have worse outcome than white men after radical prostatectomy. Therefore, we recommend that the PSA cutoff for biopsy should not be higher for black men at any age range.

Black or African American↗
PubMed1999

Role of radical prostatectomy in patients with prostate cancer of high Gleason score.

BACKGROUND: The routine use of serum prostate-specific antigen (PSA) testing combined with digital rectal examination has lowered tumor volume and clinical-pathological stage of men undergoing radical prostatectomy. Therefore, we may identify more men with poorly differentiated tumors of early clinical stage. In order to identify those who may benefit from radical prostatectomy, we evaluated known prognostic variables in patients with prostate cancer of high Gleason score (8-10). METHODS: Of 652 patients who underwent a radical prostatectomy as monotherapy for clinically localized prostate cancer between March 1991-December 1995, 84 patients with prostatectomy specimen Gleason score 8-10 tumors were identified. Clinical-pathological data were obtained from our prostate cancer database. Gleason score, PSA level, margin status, pathologic stage, and tumor volume were analyzed as general prognostic variables for disease-free survival (DFS). Follow-up ranged from 13-84 months (median, 36.2). Biochemical recurrence was defined as a postoperative PSA elevation greater than 0.4 ng/ml. RESULTS: The DFS for patients with Gleason score 8-10 and pathologically organ-confined disease was 62.5%. DFS was 56.2% for patients with PSA < or =10 ng/ml, compared to 19.2% for patients with serum PSA >10 ng/ml (P = 0.009). Patients with nonspecimen-confined disease (positive margins) had a DFS rate of 26.6% vs. 55% for patients with specimen-confined disease (negative margins) (P = 0.009). On multivariable analysis, only preoperative PSA < or =10 ng/ml (P = 0.02) and surgical margin status (P = 0.04) were significant predictors of DFS. CONCLUSIONS: Surgical margin status and preoperative serum PSA level are independent predictors of DFS for patients with high Gleason score prostate cancer treated by radical prostatectomy as monotherapy. Patients with poorly differentiated prostate cancer treated surgically at an early stage can have a favorable prognosis, especially if negative surgical margins are obtained. A preoperative serum PSA level < or =10 ng/ml carries the greatest likelihood of achieving prolonged DFS in this group of patients.

Adult↗
PubMed1999

Should African-American men be tested for prostate carcinoma at an earlier age than white men?

BACKGROUND: There have recently been challenges to testing high risk populations, i.e., African-American men younger than 50 years, for prostate carcinoma (PCa). The mortality rate of patients with PCa between ages 40 and 60 years is nearly 3 times greater among African-American men (AAM) compared with white men (WM). The literature in support of testing AAM at an earlier age than WM is sparse. Therefore, the authors present clinical and histologic data that support the testing of AAM at a younger age, utilizing data on patients with clinically localized PCa. METHODS: Examination of consecutive radical prostatectomy specimens from AAM and WM was performed from January 1991 to June 1996 among AAM and WM at Wayne State University, Harper Hospital, Detroit, Michigan. International, salvage prostatectomy, and neoadjuvant hormonal therapy patients were excluded, as were patients with lymph node metastasis. The authors examined biochemical recurrences of PCa in this cohort of men treated from January 1991 through December 1995. Univariate analysis of contingency tables was performed, using chi-squared-tests to assess the correlation between stage and race after stratification of patients by age group. Biochemical recurrence was analyzed using the Kaplan-Meier method and the log rank test. RESULTS: The authors examined radical prostatectomy specimens from 759 patients and biochemical recurrence outcome of 655 patients. AAM patients ages 50-69 years had higher prostate specific antigen levels, worse Gleason scores, more advanced stages of disease, and a higher recurrence rate. However, among men ages 70-79 years, there was no difference in these parameters between AAM and WM. Among men ages 40-49 years, a larger sample size is necessary to make meaningful comparisons. CONCLUSIONS: Data on the outcomes of men treated for clinically localized PCa demonstrated more advanced disease and more frequent recurrence among young AAM than among WM, young and of advanced age. These differences in disease severity and recurrence, in addition to the disproportionate mortality among young AAM, are strong evidence that AAM should be tested for PCa at an earlier age than WM.

Black or African American↗
PubMed1999

Long-term survival after radiotherapy alone: radiation therapy oncology group prostate cancer trials.

PURPOSE: We assess the relative importance of the several pretreatment characteristics in predicting death from prostate cancer in patients treated with curative intent with external beam radiotherapy alone. MATERIALS AND METHODS: Patients entered on 4 prospective phase III randomized trials conducted by the Radiation Therapy Oncology Group between 1975 and 1992 were selected for this analysis if they were deemed evaluable and eligible for the trial, they had received no hormonal therapy with initial treatment and followup information was available. A disease specific survival event was declared if death was certified as due to prostate cancer, complications of treatment or unknown causes with clinically active malignancy. Median followup for patients treated on early and late studies exceeded 11 and 6 years, respectively. RESULTS: Most of the patients (1,557) had tumors clinically staged as T3 (59%), and 87 (36%) with clinically staged T1-2 tumors had pathologically positive lymph nodes. On multivariate analysis Gleason score, clinical stage and nodal status were associated with a less favorable overall and disease specific survival, whereas others factors, such as age and race, were not. A Gleason score of 8 to 10 was associated with a high risk of dying of prostate cancer in the first 5 years (risk ratio 20.0, p = 0.0001). The 10-year disease specific survival for patients with a Gleason score of 2 to 5, 6 to 7 and 8 to 10 was 87, 75 and 44%, respectively, following radiotherapy. Based on published reports these rates were higher than expected with observation alone. CONCLUSIONS: In the first 10 years Gleason score was the single most important predictor of death. Gleason score should be incorporated into the current clinical staging system.

Aged↗
PubMed1999

Population-based study of pelvic lymph node positivity in clinically localized prostate cancer: a study comparing African Americans and whites.

OBJECTIVES: To evaluate the correlation between race and lymph node metastasis for prostate cancer by analyzing which preoperative parameters may predict lymph node status in both races. METHODS: We analyzed a group of patients (552 American white men [AWM] and 423 African-American men [AAM]) who underwent radical prostatectomy plus modified pelvic lymphadenectomy between January 1991 and June 1997. Patients who received neoadjuvant radiation or hormone therapy were excluded. Univariate and multivariate analyses were performed to determine the influence of race on lymph node positivity, as well as to correlate the preoperative parameters (serum prostate-specific antigen [PSA], biopsy Gleason score, and clinical stage) with lymph node metastasis for each race separately. RESULTS: The AAM presented with significantly higher preoperative Gleason scores and PSA levels than AWM. However, comparing lymph node status by race, the difference of positivity (41 AWM [7.4% and 22 AAM [5.2%]) was not statistically significant (P = 0.16). The percentage of positive nodes was similar in both races for each subset of PSA, Gleason score, and clinical stage. Despite the statistical significance of the three preoperative parameters in univariate analysis, in multivariate analysis only PSA and Gleason score were independent predictors of positive lymph nodes. CONCLUSIONS: There is no influence of race on lymph node metastasis, despite AAM presenting with higher preoperative Gleason scores and PSA levels. In multivariate analysis, preoperative Gleason score and PSA were independent factors for positive nodes regardless of race.

Black People↗
PubMed1999

Vesicourethral anastomosis biopsy after radical prostatectomy: predictive value of prostate-specific antigen and pathologic stage.

OBJECTIVES: To assess the role of clinical parameters and pathologic stage in predicting a positive vesicourethral anastomosis (VUA) biopsy in patients with a rising prostate-specific antigen (PSA) level after radical prostatectomy. METHODS: Forty-five patients were referred for a rising PSA level after radical prostatectomy. Transrectal ultrasound evaluation included visualization of the VUA and VUA quadrant biopsies. The rate of positive biopsies (per core and per patient) was correlated with race, PSA level, and the radical prostatectomy pathologic stage. RESULTS: Overall, 53% of patients had a positive biopsy. In multivariate analysis, the dominant independent and synergistic clinical parameters determining positive biopsy rates were a PSA greater than 1 ng/mL at the time of biopsy and the pathologic stage (P = 0.04 and P = 0.02, respectively). Using a PSA cutoff point of 1.0 ng/mL, those patients with organ-confined disease and a PSA of 1.0 ng/mL or less showed no positive cancer cores (low-risk group). Conversely, 89% of patients with extraprostatic extension and a PSA greater than 1.0 ng/mL had a positive biopsy (P <0.01) (high-risk group). Patients with organ-confined disease and a PSA greater than 1.0 ng/mL or extraprostatic extension and a PSA 1.0 ng/mL or less (intermediate-risk group) had a significantly higher chance of having residual cancer than the low-risk group (P <0.025). CONCLUSIONS: The PSA level at the time of biopsy and the pathologic stage of the radical prostatectomy specimen were the strongest determinants of a positive biopsy. A combination of PSA and pathologic stage is useful for decisions regarding VUA biopsy. Patients with organ-confined disease and a PSA of 1.0 ng/mL or less do not appear to benefit from a VUA biopsy, and patients with extraprostatic extension and a PSA greater than 1.0 ng/mL have such a high probability (89%) of local recurrence at the VUA that biopsy may be unnecessary. It appears that VUA biopsy can be restricted to those patients with an intermediate risk (organ-confined disease with PSA greater than 1 ng/mL or extraprostatic extension with a PSA less than 1 ng/mL).

Aged↗
PubMed1998

Identification of a novel truncated alphaIIb integrin.

Integrin alphaIIb beta3 requires its cytoplasmic tails to participate in tumor cell adhesion, spreading, and migration. Using 3' rapid amplification of cDNA ends, we have amplified two alphaIIb cDNAs from human leukemia, prostate adenocarcinoma, and melanoma cells. One of these is the predicted wild-type alphaIIb cDNA, and the other is a novel truncated alphaIIb variant. This variant is unique in that it lacks the transmembrane and cytoplasmic portions of the alphaIIb light chain. The truncated alphaIIb integrin protein is expressed by human leukemia, prostate adenocarcinoma, and melanoma cells but not by platelets or normal prostate epithelial or normal breast epithelial cells. Tumor cells secrete this protein and deposit it on the extracellular matrix. To our knowledge, this is the first report of a naturally occurring variant of an alpha integrin that lacks the transmembrane and cytoplasmic tail.

Alternative Splicing↗
PubMed1998

Correlation of color Doppler flow in the prostate with tissue microvascularity.

BACKGROUND: The pathophysiology of increased color Doppler (CD) flow has not previously been addressed in histologic evaluations of microvascular parameters. In this study, the authors attempted to define the differences between benign and malignant biopsy cores found in regions of the prostate with normal and high CD flow. METHODS: Forty patients were retrospectively chosen for CD histologic comparison, each of whom had a core from a sextant biopsy with the following characteristics: malignant tissue with distinct increased CD flow (n=11), malignant tissue with normal CD flow (n=10), benign tissue with distinctly increased CD flow (n=9), or benign tissue with normal CD flow (n=10). All biopsy cores were stained with factor VIII-related antigen to identify microvasculature and to determine the number of microvessels per square millimeter (mm2) in an average cross-sectional area of microvessels, the percentage of tissue occupied by microvasculature, and the Gleason score. RESULTS: In biopsies of benign tissue, high CD flow was associated with greater numbers (P < 0.025) of vessels of similar size than in normal flow benign biopsies. Biopsies of malignant tissue contained significantly greater numbers (P < 0.01) of much smaller vessels (P < 0.0005) than biopsies of benign tissue. In biopsies of malignant tissue, no significant differences in microvasculature parameters were noted between high and normal CD flow, yet biopsies with high CD flow had average Gleason score of 6.7 compared with only 5.9 for biopsies with normal CD flow (P < 0.025). CONCLUSIONS: Increased CD flow in biopsies of benign tissue was correlated with a greater number of vessels/mm2, yet all biopsies of malignant tissue had more vessels/mm2 than those of benign tissue. Increased CD flow in biopsies of malignant tissue cannot be explained by standard microvasculature analysis but significantly guides biopsies to regions with a greater Gleason score.

Humans↗
PubMed1998

Predictors for maximal outcome in patients undergoing salvage surgery for radio-recurrent prostate cancer.

OBJECTIVES: To determine preradiation and preoperative clinical staging and postoperative pathologic factors that can predict disease-free survival in patients undergoing salvage surgery for radio-recurrent prostate cancer. METHODS: A retrospective review was performed on 40 patients who underwent salvage surgery for radio-recurrent prostate cancer. Preradiation and preoperative clinical staging factors, as well as pathologic stage were analyzed as predictors of disease-free survival. Biochemical failure was defined as a persistent serum prostate-specific antigen (PSA) elevation greater than 0.4 ng/mL. RESULTS: As a group, salvage surgery provided excellent clinical disease control in 35 of 40 patients (87.5%). Overall, 18 of 38 (47.4%) patients analyzed had no evidence of biochemical progression. Preradiation clinical stage and pathologically organ-confined disease were statistically significant predictors of disease-free survival (P = 0.03 and P = 0.02, respectively). Seminal vesicle invasion and positive lymph nodes were the worst pathologic prognostic factors. Preoperative clinical T1c disease approached statistical significance in predicting pathologically organ-confined disease and disease-free survival (P = 0.08 and P = 0.07, respectively). CONCLUSIONS: Ideal candidates for salvage surgery should have preradiation and preoperative clinically organ-confined disease. All patients with pathologically organ-confined disease following salvage prostatectomy were disease free at a mean follow-up of 36.1 months. Salvage surgery, although technically feasible, should not be widely advocated as an effective curative treatment in patients with locally advanced disease at the time of diagnosis.

Adenocarcinoma↗
PubMed1998

Primary adenocarcinoma of the urethra with metastasis to the glans penis: successful treatment with chemotherapy and radiation therapy.

Primary carcinoma of the male urethra accounts for less than 1% of malignancies in males. A 54-year-old man with primary adenocarcinoma of the urethra with metastasis to the glans penis and lymphadenopathy in the right groin was treated successfully by combined chemotherapy (5-fluorouracil and cis-platinum) and external beam radiotherapy (total dose of 75 Gy). Short-term remission using multimodal approach with penile preservation was achieved in the present case.

Adenocarcinoma↗
PubMed1998

Cancer as a marker of genetic medical disease: an unusual case of medullary carcinoma of the kidney.

Medullary carcinoma is a recently recognized tumor of the kidney with distinctive microscopic features; the most notable are diffuse and glandular growth patterns, inflammatory infiltrates, and rhabdoid/plasmacytoid cells. It is a clinically aggressive tumor that occurs in relatively young patients. Moreover, this tumor shows a peculiar clinical association: it occurs in patients with sickle cell hemoglobinopathy. The case presented is that of a 37-year-old black woman with a history of bronchial asthma who died suddenly. Autopsy showed a 4-cm renal mass with extension to the inferior vena cava and metastases to the liver. Histologic evaluation showed the characteristic findings of medullary carcinoma of the kidney. This diagnosis prompted the investigation and subsequent detection of sickle cell trait in the deceased, alerting the family to the genetic nature of her illness. This case is the first report of this entity since the original described series of patients and shows the unique nature of this cancer as a marker of a genetic medical disease.

Adult↗
PubMed1997

Frequent breakpoints in the region surrounding FRA3B in sporadic renal cell carcinomas.

The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is the most active common fragile site in the human genome. We have localized aphidicolin-induced breakpoints to two distinct clusters, separated by 200 Kb, in FRA3B (Paradee et al., 1996). Sequence analysis of these regions identified two polymorphic microsatellite markers immediately adjacent to each of these breakpoint clusters. In this report we have used these two new microsatellites and 14 additional 3p microsatellites to analyse chromosome 3p breakage and loss in 94 sporadic RCC samples, including nonpapillary, papillary and oncocytomas. We have found heterozygous loss of 3p14 sequences in >60% of the RCC samples, including both clear cell and papillary renal cell carcinomas. We have found frequent breakage in the region immediately surrounding FRA3B, demonstrating that FRA3B does play a role in chromosome breakage and loss in RCC. In contrast to other reports, >50% of the papillary tumors also showed LOH of 3p markers. We also observed microsatellite instability (MIN) with most of the tested markers in seven of eight oncocytomas and one of 69 clear cell carcinomas. The MIN in some oncocytomas was of the RER+ (replication error) type I phenotype. None of the five 3p14.2 markers detected any homozygous deletions in tumor samples, but 69/94 (73%) of the tumors had LOH for the region, which includes the recently identified FHIT gene.

Adult↗