Biomedical subjects

Thomas J Sebo

Publications and source records attributed to Thomas J Sebo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Monitoring intravesical therapy for superficial bladder cancer using fluorescence in situ hybridization.

PURPOSE: We evaluated fluorescence in situ hybridization (FISH) for assessing the response to therapy in patients with superficial bladder cancer receiving bacillus Calmette-Guerin or other intravesical therapies. MATERIALS AND METHODS: A total of 37 patients receiving intravesical therapy for superficial bladder cancer were enrolled in this study. Urine specimens were collected for FISH analysis just prior to the first intravesical therapy in 31 cases and just prior to or within 2 months following the last intravesical therapy in 37. FISH was done using the UroVysion probe set (Abbott Laboratories, Abbott Park, Illinois) with results considered positive if 5 or more cells demonstrated polysomy. Biopsy, cystoscopy and/or cytology results were then compared to FISH results to evaluate the usefulness of the test for monitoring intravesical therapy. RESULTS: Of the patients 25 had a negative and 12 had a positive post-therapy FISH result. All 12 patients with a positive post-therapy FISH result had tumor recurrence, while tumor recurrence was observed in 13 of the 25 with a negative post-therapy FISH result (HR 4.6, 95% CI 1.9 to 11.1, p <0.001). Of the patients with tumor recurrence 7 of 12 with a positive post-therapy FISH result had muscle invasive tumor and 2 of 25 with a negative post-therapy FISH result had muscle invasive tumor (HR 9.4, 95% CI 1.9 to 45.3, p = 0.001). CONCLUSIONS: FISH appears to be useful for monitoring patients with superficial bladder cancer for the response to intravesical therapy. Patients with a positive FISH result at the end of treatment are at high risk for progression to muscle invasive bladder cancer.

Adjuvants, Immunologic↗

PubMed2005

The extent of lymphadenectomy for pTXNO prostate cancer does not affect prostate cancer outcome in the prostate specific antigen era.

PURPOSE: Recent data suggest that extended lymph node dissection in prostate cancer may be necessary for accurate staging. With limited lymph node dissection apparently node negative cases might be under staged. We determined the impact that the number of lymph nodes removed at radical retropubic prostatectomy (RRP) has on cancer progression and cause specific survival in pTXNO cases. MATERIALS AND METHODS: We reviewed the RRP prostate cancer database on 7,036 patients with clinical T1 to T3 disease, no adjuvant therapy and node negative disease in the prostate specific antigen (PSA) era from 1987 to 2000. Factors evaluated were the number of lymph nodes obtained at RRP, preoperative PSA, clinical and pathological stage and grade, margin status, year of surgery and specific surgeon for 5 surgeons who operated throughout the period and performed more than 500 RRPs. Cox analysis was done to determine the RR of progression (PSA or systemic) and prostate cancer death for the number of lymph nodes excised. RESULTS: Median patient age was 65 years and median preoperative PSA was 6.6 ng/ml. At pathological evaluation 5,379 tumors (77%) were organ confined, 4,491 (65%) were Gleason score 5 to 6 and 2,027 (29%) were Gleason score 7 to 10. The median number of nodes obtained significantly decreased from 14 in 1987 to 1989 to 5 in 1999 to 2000 (p <0.001). Ten years after RRP Kaplan-Meier estimates were 63% of cases free of PSA progression, 95% free of systemic progression and 98% free of prostate cancer related death. Median followup was 5.9 years. After adjusting for pathological factors (PSA, grade, stage, margin status and surgical date) the number of lymph nodes obtained at lymphadenectomy was not significantly associated with PSA progression (for each additional node (RR 0.99, 95% CI 0.98 to 1.02, p = 0.90), systemic progression (RR 0.99, 95% CI 0.96 to 1.03, p = 0.68) or cause specific survival (RR 1.01, 95% CI 0.96 to 1.06, p = 0.75). CONCLUSIONS: The extent of lymphadenectomy does not appear to affect prostate cancer outcome in lymph node negative cases. This includes patients with high preoperative PSA, high pathological grade and extracapsular disease. These results suggest that under staging is not present in apparently node negative cases with limited lymphadenectomy and, even if present, its impact on outcome is likely to be negligible.

Adult↗

PubMed2005

Salvage surgery for radiorecurrent prostate cancer: contemporary outcomes.

PURPOSE: We present a 30-year experience with performing salvage surgery in patients with persistent prostate cancer (PCA) after definitive radiotherapy. MATERIALS AND METHODS: Patients with biopsy proven PCA following definitive radiotherapy who underwent salvage surgery were identified retrospectively (1967 to 2000). Prostate specimens were evaluated by a single pathologist. Progression-free survival (PFS) and cancer specific survival (CSS) estimates were made with multivariate analysis of outcome predictors. Complications were reviewed. RESULTS: Sufficient information was available on 199 patients, including 138 with retropubic prostatectomy (RP) and 61 with cystoprostatectomies (CP). Median followup was 7.0 years. Rectal injury rates (5% for RP and 10% for CP) remained stable, while transfused units of blood decreased. Urinary extravasation (15% of cases) and bladder neck contracture (22%) were the most common complications. Urinary continence (0 pads) improved from 43% to 56% of patients (p = 0.17) with an additional 20% requiring 1 or fewer pad daily. Overall 10-year CSS in all patients undergoing salvage surgery was 65%. Patients undergoing RP fared better than those needing CP (10-year CSS 77% vs 38%, p <0.001 and median PFS 8.7 vs. 4.4 years, p <0.001). Tumor ploidy, percent 4/5 Gleason grade and pathological stage were strong predictors of outcome, while margin status and preoperative prostate specific antigen had minimal predictive strength. CONCLUSIONS: Significant PFS and CSS can be expected following salvage surgery for radioresistant PCA. Several pathological features of the removed prostate are predictive of survival. The surgical risks of salvage surgery are now defined. Morbidity rates, including continence, have moderately improved with time.

Aged↗

PubMed2005

Sonography of thyroid nodules: a "classic pattern" diagnostic approach.

This article describes an approach to some of the commonly encountered, "classic pattern," appearances of both benign and malignant thyroid nodules that are seen in day-to-day practice. These appearances include specific nodules that commonly need fine needle aspiration (FNA)/biopsy, and other nodules that do not usually need FNA/biopsy.

Biopsy, Fine-Needle↗

PubMed2005

Analysis of polyomavirus-infected renal transplant recipients' urine specimens: correlation of routine urine cytology, fluorescence in situ hybridization, and digital image analysis.

Urinary polyomavirus subtype BK (BKV)-infected urothelial and renal tubular cells, "decoy cells," have been shown to be aneuploid with digital image analysis (DIA). We wanted to determine whether decoy cells cause false-positive fluorescence in situ hybridization (FISH) results in BKV-infected urine samples. Urine samples from 38 renal transplant recipients were split 3 ways and evaluated for number of decoy cells per 10 high-power fields by routine cytology, total nuclear DNA content by DIA, and chromosomal abnormalities by FISH. For DIA, Feulgen-stained cells were quantified with a CAS 200 image analyzer (Bacus Laboratories, Lombard, IL), and for FISH, the UroVysion probe set (Vysis, Downers Grove, IL) consisting of chromosome enumeration probes 3, 7, 17, and locus-specific identifier probe 9p21 (p16 gene) was used. Of the 38 specimens, 32 (84.2%) had evidence of BKV infection by routine cytology. DIA and FISH results were aneuploid/aneusomic in 30 (93.8%) and 4 (12.5%) cases, respectively. All aneusomic FISH specimens occurred in men older than 52 years of age and who also had 4 of the 6 highest PCR-BKV titers. To date, no patient has clinical evidence of malignancy. The 6 specimens without decoy cells were DNA diploid/disomic by DIA and FISH. Abnormal FISH results of urinary decoy cells occur much less frequently than aneuploidy by DIA in renal transplant recipients and might merit close follow-up in some transplant recipients.

Adult↗

PubMed2005

A systematic approach to identifying urothelial cells likely to be polysomic by fluorescence in situ hybridization.

OBJECTIVE: To determine which nuclear morphologic and background features are most associated with normal and abnormal chromosome patterns in urine cells evaluated by fluorescence in situ hybridization (FISH) with Vysis UroVysion (Downers Grove, Illinois, USA). STUDY DESIGN: One hundred specimens were analyzed and the nuclear morphologic and background features compared between FISH-negative (disomic) and -positive (polysomic) cases. RESULTS: Our data show that polysomic urothelial cells have significantly (p < 0.001) weaker DAPI nuclear counterstaining, nuclear enlargement, more irregular nuclear shape and more chromatin clumping when compared to disomic cells. CONCLUSION: These findings indicate that there are specific staining and nuclear cytologic features that can help identify cells that have a high probability of being polysomic by FISH. This information may help cytologists decrease the time required to evaluate urine specimens by FISH and may aid in the development of instruments that automate FISH analysis.

Adult↗

PubMed2004

Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement.

BACKGROUND: The effect of p53 protein expression and MIB-1 proliferative activity on survival and chemotherapeutic response in patients with lymph node (LN)-positive transitional cell carcinoma (TCC) of the urinary bladder remains unclear. The objective of this study was to assess the ability of these markers to predict disease-associated outcomes and response to chemotherapy in a cohort of patients with LN-positive TCC. METHODS: The authors examined the expression of p53 and MIB-1 in the LN metastases from 139 patients who underwent cystectomy for TCC at their institution. P53 and MIB-1 nuclear staining were quantified using an image-analysis system. Cox proportional hazards regression models were used to test associations of these markers with death from TCC, distant metastases, and local recurrence for all patients and in the subset of patients who were treated with adjuvant chemotherapy. RESULTS: The median p53 and MIB-1 indices were 45.2% and 30.3%, respectively. The median follow-up was 4.5 years (range, 0.1-10 years). There were no statistically significant associations noted between the p53 and MIB-1 indices and the outcomes studied. When the analysis was limited to patients who were treated with adjuvant chemotherapy (n = 37 patients), the p53 index was found to have no prognostic value; however, there was a significant association between MIB-1 and distant metastases (P = 0.049). When disease-specific survival rates were stratified according to p53 index and chemotherapy, patients exhibited a response to chemotherapy regardless of p53 index. CONCLUSIONS: p53 and MIB-1 were not found to be associated significantly with disease-related outcomes in patients with LN-positive TCC. Adjuvant chemotherapy appeared to be effective regardless of p53 status. MIB-1 may prove useful in predicting response to chemotherapy.

Biomarkers, Tumor↗

PubMed2004

PPARgamma staining as a surrogate for PAX8/PPARgamma fusion oncogene expression in follicular neoplasms: clinicopathological correlation and histopathological diagnostic value.

The PAX8/PPARgamma (PPFP) fusion-oncogene is moderately specific for follicular thyroid carcinomas (FTC). It remains unknown whether this can be translated into improved diagnosis, classification, or outcome prediction. We studied a cohort of well-characterized follicular adenomas (FA), FTC, and Hurthle cell carcinomas (HCC) from patients with complete clinical follow-up, to determine whether PPARgamma immunohistochemistry (as a surrogate of PAX8/PPARgamma expression) helps to distinguish FA from FTC and to assess its diagnostic accuracy as an adjunct to frozen section. We also correlated PPARgamma staining with clinical outcomes to assess its role as a prognostic marker.PPARgamma staining was more common in FTC (31 of 54; 57%) than in HCC (one of 23; 4%) or FA (four of 31; 13%) (P < 0.000001). Adjunctive use of PPARgamma immunohistochemistry improved diagnostic sensitivity of intraoperative frozen section from 84% to 96% (P < 0.05) but reduced specificity from 100% to 90% (P < 0.05). PPARgamma staining was associated with favorable prognostic indicators (female gender, better tumor differentiation, and lesser risk of metastases).PPARgamma staining may be helpful in the differential diagnosis of FA, FTC, and HCC, particularly when diagnostic sensitivity of histomorphology is reduced (e.g. during intraoperative frozen section). PPARgamma staining also shows an association with favorable prognosis and may have a role in risk stratification.

Adenoma↗

PubMed2004

Fine-needle aspiration cytology findings from a case of pancreatic heterotopia at the gastroesophageal junction.

Pancreatic heterotopia is a well-recognized entity occurring at a variety of sites in the gastrointestinal tract. However, only a handful of patients have been described with this abnormality at the gastroesophageal junction. Cytologic descriptions of pancreatic heterotopia in general are scant in the literature. We report the cytologic findings of ectopic pancreatic tissue at the gastroesophageal junction in a 41-year-old female, which was initially identified by endoscopic ultrasound and fine-needle aspiration. Cytologic examination of Papanicolaou-stained smears revealed clusters of benign-appearing ducts and small acini mixed with inflammatory cells. Hematoxylin and eosin staining of the Tru-Cut biopsy revealed benign pancreatic tissue. The patient underwent surgical resection due to symptoms related to inflammation of the heterotopic pancreatic tissue. The increasing use of endoscopic ultrasound and fine-needle aspiration for the diagnosis of gastrointestinal tumors makes the recognition of pseudoneoplastic lesions at unusual sites an important step in optimum patient management.

Adult↗

PubMed2004

Histiocytes containing immunoglobulin crystals in the urine of a patient with IgA kappa plasmacytoma of the bladder.

Exfoliative cytology specimens from patients with plasma cell dyscrasias are rarely diagnostic, though there are reports of neoplastic plasma cells observed in pleural fluid and urine. Immunoglobulin concretions or crystals associated with neoplastic plasma cell populations have been well described. These crystals may be found within plasma cell nuclei or cytoplasm, extracellularly, or within cells of histiocytic lineage where they are presumably derived by phagocytosis. To the best of our knowledge, this is the first report of immunoglobulin crystals within histiocytes in the urine of a patient with plasmacytoma. A 61-year-old male underwent routine cystoscopy and urine collection to evaluate hematuria. The bladder biopsy demonstrated IgA kappa-producing plasmacytoma. Urine cytopsin preparations did not contain plasma cells, but there were histiocytic cells with degenerative nuclei and eccentrically located cytoplasmic spherical refractile hyaline crystals thought to be immunoglobulin crystals. This was supported by immunocytochemical staining.

Crystallization↗

PubMed2004

A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures.

BACKGROUND & AIMS: Digital image analysis (DIA) allows quantification of nuclear DNA content and may help distinguish benign and malignant strictures of the biliary tract. METHODS: One hundred ten consecutive patients undergoing endoscopic retrograde cholangiography for suspicious biliary tract strictures were enrolled in a prospective study comparing the accuracy of DIA and routine cytology (RC). Standard brush cytology sampling was performed twice by using 2 cytology brushes per patient. Both brushes were fixed in a single-specimen vial. Each specimen was formed into 1 pellet, and the sample was equally divided for evaluation by DIA and RC. DNA histograms were generated for ploidy analysis. The DIA criterion for malignancy was demonstration of aneuploidy. RESULTS: Two patients had inadequate samples obtained for DIA analysis, 7 benign patients were excluded because of inadequate follow-up of less than 75 days, and 1 patient was lost to follow-up to clarify malignant versus benign disease. Of the remaining 100 patients, 56 strictures were malignant and 44 were benign. The sensitivities of DIA and RC were 39.3% and 17.9%, respectively (P = 0.014). The specificities of DIA and RC were 77.3% and 97.7%, respectively (P = 0.003). The accuracy of DIA (56.0%) was equivalent to RC (53.0%). CONCLUSIONS: DIA is a valuable adjunct to RC for detecting malignant strictures of the biliary tract.

Adult↗

PubMed2004

Hyalinizing trabecular adenoma of the thyroid gland: cytologic features in 29 cases.

Cytologic material (fine-needle aspiration biopsy smears, thin-layer preparations, cell block sections, and touch preparations) from 29 cases of hyalinizing trabecular adenoma was studied to 1) establish the cytologic profile of the neoplasm and 2) compare the profile with those of papillary and medullary carcinoma. Papanicolaou- and Diff-Quik-stained smears of the hyalinizing trabecular adenomas were uniformly bloody. The smears featured cells in cohesive aggregates radially oriented around hyaline material, less frequently, singly. Cytoplasm was abundant, and the nucleocytoplasmic ratio was low. Intranuclear cytoplasmic inclusions, nuclear grooves, and nuclear overlapping were very common and best seen with the Papanicolaou method. Diff-Quik-stained smears highlighted the hyaline material (metachromatic), perinucleolar clearing, and cytoplasmic bodies. The combination of a bloody background, radially oriented cohesive cells, cells with abundant cytoplasm, nuclei with very frequent cytoplasmic inclusions and grooves, and the presence of hyalin should suggest the presence of hyalinizing trabecular adenoma.

Adenoma↗

PubMed2004

Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma.

The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.

Carcinoma, Papillary, Follicular↗

PubMed2004

A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures.

BACKGROUND AND AIM: The aim of this study was to assess the relative sensitivities and specificities of fluorescence in situ hybridization (FISH) and routine cytology for the detection of malignancy in biliary tract strictures. METHODS: Bile duct brushing and aspirate specimens were collected from 131 patients being evaluated for possible malignant bile duct strictures. Both specimen types were assessed by FISH but only brushing specimens were assessed by cytology. The FISH assay used a mixture of fluorescently-labeled probes to the centromeres of chromosomes 3, 7, and 17 and chromosomal band 9p21 (Vysis UroVysion) to identify cells having chromosomal abnormalities. A case was considered positive for malignancy if five or more cells exhibited polysomy. RESULTS: Sixty-six of the 131 patients had surgical pathologic and/or clinical evidence of malignancy. Thirty-nine patients had cholangiocarcinoma, 19 had pancreatic carcinoma, and 8 had other types of malignancy. The sensitivity of cytology and FISH for the detection of malignancy in bile duct brushing specimens in these patients was 15% and 34% (p < 0.01), respectively. The sensitivity of FISH for the bile aspirate specimens was 23%, and the combined sensitivity of FISH for aspirate and brushing specimens was 35%. The specificity of FISH and cytology brushings were 91% and 98% (p= 0.06), respectively. CONCLUSIONS: FISH is significantly more sensitive than and nearly as specific as conventional cytology for the detection of malignant biliary strictures in biliary brushing specimens. FISH may improve the clinical management of patients who are being evaluated for malignancy in bile duct strictures.

Adolescent↗

PubMed2004

Prospective, blinded assessment of factors influencing the accuracy of biliary cytology interpretation.

OBJECTIVES: There is little published data assessing factors that influence the accuracy of biliary cytology. The aim of this study was to (a) prospectively compare interobserver variability among two blinded pathologists interpreting biliary cytology specimens, (b) to describe the predictors of interpathologist agreement, and (c) to characterize the predictors of accurate cytology interpretation. METHODS: In total, 113 consecutive patients undergoing endoscopic retrograde cholangiopancreatography with brushing of suspicious biliary tract strictures were prospectively enrolled to assess routine cytology (RC) accuracy. The initial RC interpretation was performed by the pathologist on duty with the benefit of the patient's clinical information. Subsequent interpretation was performed by two independent pathologists blinded to the patients' clinical details. RESULTS: Of the 113 patients, 67 had malignant strictures and 46 had benign strictures. The sensitivity of RC varied from 9% to 24% (p= 0.02), while the specificity varied from 61% to 100% (p < 0.001). Accuracy varied from 43% to 51% (p= n.s.). The rate of equivocal readings was lowest for the initial interpretation (1.7%), p < 0.0001 versus pathologist 1, p= 0.002 versus pathologist 2. Overall correlation of the blinded pathologists' interpretations was moderate, k= 0.66. Neither cytology accuracy nor interpathologist agreement improved with increasing specimen cellularity. CONCLUSIONS: There is a high rate of interpathologist variation for the biliary cytology interpretation. The knowledge of the patient's clinical information appears to clarify cytology interpretation resulting in fewer equivocal results. We did not detect any reliable predictors of cytology accuracy.

Bile Duct Neoplasms↗

PubMed2004

Hyalinizing trabecular adenoma of the thyroid gland identification through MIB-1 staining of fine-needle aspiration biopsy smears.

Smears of fine-needle aspiration (FNA) biopsy specimens of 24 histologically proven and MIB-1-positive hyalinizing trabecular adenomas stained with Papanicolaou or Diff-Quik were stripped from the original slides, transferred to charged slides, destained, and restained with MIB-1. Positive immunoreactivity with MIB-1 in a peripheral cytoplasmic pattern was present in 17 specimens, no immunoreactivity was seen in 4 specimens, and equivocal staining was seen in 3 specimens. Papanicolaou-stained smears of papillary thyroid carcinoma, medullary thyroid carcinoma, thyroid follicular neoplasm, and Hürthle cell adenoma (5 specimens each) were treated similarly. None of the control cases stained with MIB-1 had the peripheral cytoplasmic pattern. Hyalinizing trabecular adenoma can be distinguished reliably from other thyroid neoplasms by MIB-1 staining of destained cells from FNA biopsy specimens.

Adenoma↗

PubMed2004

An analysis of the p63/alpha-methylacyl coenzyme A racemase immunohistochemical cocktail stain in prostate needle biopsy specimens and tissue microarrays.

We studied the usefulness of a p63/P504S immunostain "cocktail" in evaluation of prostate biopsy specimens containing atypical acini suspicious for adenocarcinoma (AASA), high-grade prostatic intraepithelial neoplasia (HPIN), and small foci of adenocarcinoma and tested the sensitivity and specificity of the immunostain with tissue microarrays (TMAs) constructed from prostatectomy and lymphadenectomy specimens. We selected 40 cases containing a focus of adenocarcinoma (14 cases), AASA (7 cases), AASA with HPIN (7 cases), HPIN (6 cases), and atypical favor benign (6 cases). After p63/P504S immunostaining, 13 cases (33%) were reclassified: AASA with HPIN to HPIN only in 5 cases (13%), atypical favor benign to benign in 4 cases (10%), AASA to adenocarcinoma in 2 cases (5%), and atypical favor benign to AASA and atypical favor benign to HPIN in 1 case (3%) each. The diagnosis of adenocarcinoma was supported by immunostain in 14 cases. In TMA studies, the p63/P504S immunostain for adenocarcinoma and HPIN had sensitivity values of 97.2% and 86.2%, respectively, and specificity values of 99.7% and 81.6%, respectively. P504S stained 64 (74%) of 87 cores of metastatic cancers, and no p63-positive cells were identified in the metastases. The p63/P504S immunohistochemical stain is a sensitive, specific marker for prostatic adenocarcinoma and HPIN and useful in the evaluation of AASA in biopsy specimens.

Adenocarcinoma↗

PubMed2003

Microsatellite instability in hereditary and sporadic breast cancers.

Sporadic cancers and familial breast cancers are characterized by an increase in genetic instability. Little is known about whether mismatch repair defects accompany this genetic instability. We investigated invasive and/or in situ breast cancers from 30 women with deleterious BRCA1/2 mutations and unclassified variant BRCA1/2 alterations. Forty cases of sporadic breast cancers were also investigated, including 7 medullary carcinomas. Malignant and benign lesions were examined from all cases to better understand tumor progression. Automated immunohistochemistry, with antibodies directed against hMLH1 and hMSH2, was used to screen cases for possible mismatch repair defects. When loss of expression was noted, DNA ploidy was performed by cytomorphometry. DNA, after laser microdissection, was extracted from a majority of familial cases and their corresponding controls, and microsatellite instability analysis was performed. None of the familial or sporadic cases had loss of hMSH2 expression. All but one lesion, a DCIS arising in a deleterious BRCA2 mutation carrier, had loss of hMLH1 expression and a tetraploid profile by image cytomorphometry. There was no MSI in any explored lesions (n = 34), as determined by molecular analysis, including the DCIS with loss of hMLH1 expression. We conclude that DNA mismatch repair defects involving hMLH1 and hMSH2 underexpression are extremely rare events in sporadic and familial breast cancer. Mismatch repair gene mutations may be secondary random events in breast cancer progression.

Adaptor Proteins, Signal Transducing↗