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PubMedDate not supplied

Detection of non-papillary, non-invasive transitional cell G1 carcinoma as revealed by increased DNA instability and other cancer markers.

The method to reveal DNA-instability as demonstrated by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) was used as a marker of malignancy. The test was applied to paraffin-embedded sections taken from 15 urinary bladders, renal pelvic cavities, and ureters bearing multiple carcinoma in situ (CIS) and totally 31 papillary urothelial cancers. The serial sections of the same tissues were also subjected to immunohistochemical staining for PCNA, p53, DFF45, and VEGF. The DNA-instability test was positive in 100% cancer lesions irrespective of the grades, and apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions also showed the areas with clones positively stained with DNA-instability testing, and the percent numbers of positive areas in them were 28.3%, 37.7%, and 61.5%, respectively. These clones, which were present in apparently normal urothelium and in hyperplastic and dysplastic urothelial lesions, showed higher percent values of PCNA-positive-cells, in comparison to the values estimated in the areas with negatively stained DNA-instability testing, and the former values were statistically not different from those in carcinoma lesions. Furthermore, the percent numbers of areas positive for p53, DFF45, and VEGF, with positive DNA-instability testing were also much higher than those with negative DNA-instability testing in apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions, and the former values were again comparable to those in cancer lesions with no statistical differences. These clones were regarded as already being malignant and should be the direct precursors of progressed cancer lesions. They will make progression through two different pathways, one to papillary non-invasive G1 cancers by neovascularization induced by paracrine secretion of VEGF, and another to flat CIS G2 without secretion of VEGF; thus the clones should be regarded as non-papillary, non-invasive Gl TCC, or CIS G1. It should be always taken into account that the probability for apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions to contain cancer clones, will be high already, especially in tumor-bearing bladders.

Biomarkers, Tumor↗
PubMed2005

Recurrent anterior glenohumeral instability with onset after forty years of age: the role of the anterior mechanism.

Recurrent instability in patients over forty years of age is felt to occur primarily as a result of an associated rotator cuff tear. This is often referred to as the "posterior mechanism." We reviewed our patients over the age of forty who underwent an anterior shoulder repair to identify the incidence of capsulolabral detachments and the role of an "anterior mechanism" in this patient population. A retrospective review of all patients from 1985 to 2000 was performed to identify patients who had surgery for recurrent instability that began after forty years of age. Of the 265 patients records reviewed, 11 patients were identified who fulfilled the inclusion criteria. Of the 11 patients identified, 9 patients underwent anterior capsulolabral reconstruction for recurrent instability; the remaining two patients underwent repair of large rotator cuff tears. All 9 patients had a capsulolabral detachment, 4 had a rotator interval defect, 2 had anterior and inferior capsular redundancy, 1 had a small rotator cuff tear and 1 had an anterior capsular avulsion from the humeral head. At minimum follow-up of 32 months none of the patients reported episodes of instability. The reported incidence of rotator cuff tears in patients over the age of forty following an initial traumatic anterior glenohumeral dislocation ranges from 35% to 100%. When recurrent instability occurs, it is postulated to occur via a "posterior mechanism" (i.e., secondary to a significant full-thickness rotator cuff tear). However, all of our patients had an anterior capsulolabral detachment as the "common lesion" associated with recurrent instability. Although small, this series emphasizes the role of the "anterior mechanism" in patients who develop recurrent instability after the age of forty. A high rate of success was achieved by addressing the pathoanatomic changes identified.

Adult↗
PubMed2005

Posterior capsulorrhaphy for treatment of recurrent posterior glenohumeral instability.

The surgical treatment of recurrent posterior shoulder instability via a posterior approach has had a variable degree of success reported in the literature with recurrence rates ranging between 8% and 45%. The purpose of this study was to review the results of posterior capsulorrhaphy in a consecutive series of patients with recurrent posterior instability. Seventeen consecutive patients underwent operative management for posterior glenohumeral instability. The dominant shoulder was involved in ten patients. All patients were male with an average age of 28.1 years (range: 16 to 54 years). Ten patients had sustained a specific injury which precipitated the instability. Six patients reported dislocations requiring formal closed reduction maneuvers; the remainder described episodes of recurrent subluxation with spontaneous reduction. All patients underwent a posterior capsulorrhaphy using an infraspinatus splitting approach. Eight shoulders required repair of a posterior capsulolabral detachment. In addition, one patient required augmentation with a posterior bone block for significant glenoid rim deficiency. Outcome was assessed by personal interview, clinical assessment, and standardized radiographs. At an average follow-up of 3.9 years (range: 1.8 to 10.8 years) patients estimated their overall shoulder function to be 81% of the contralateral unaffected shoulder. The subjective result was excellent for eight patients, good for five patients, fair in two patients, and poor in two patients. One of the poor outcomes was in a patient with glenohumeral degenerative changes at the index procedure which progressed and eventually required a total shoulder arthroplasty. The other poor result was in a patient found to have a full-thickness rotator cuff tear 10.6 years after the index procedure. Two patients (12%) had recurrence of their instability. Both of these patients sustained a significant re-injury which precipitated their symptoms. Five patients complained of occasional night pain at the time of their last follow-up examination. Only one patient (who was re-injured) had to change professions as a result of shoulder symptoms. Posterior capsulorrhaphy for treatment of isolated posterior glenohumeral instability yields satisfactory clinical results. Recurrent instability in this series was associated with a specific re-injury and did not appear to increase with longer follow-up.

Adolescent↗
PubMedDate not supplied

[Transgenerational transmission of radiation induced genomic instability].

Stability of genome is one of the evolutionary important trait of cells. Various mutations (gene, chromosomal, genomic) as well as artificial manipulations with genomes (inbreeding, DNA transfection, introduction of Br-DU in DNA) cause the genetic instability. Ionizing radiation is known as the factor which induced instability of genome in late mitotic descendants of cells after in vitro and in vivo exposure. Radiation induced genetic instability can be transmitted through germline cells. On the cell level both types of radiation induced genomic instability are manifested in elevated frequency of mutations, chromosome aberrations, micronuclei, increased radiosensitivity, disappearance of adaptive response, changes in gene expression. In studies of 1970-1980 years clear evidences on the different morphological and functional injuries in tissues of irradiated organisms as well as in tissues of the progeny of exposed parents were obtained. On the organism level the instability of mitotic and of meiotic progeny of irradiated cells is resulted in increased risk of cancer and of other somatic diseases. It seems to be useful to review the earlier radiobiology literature where delayed and transgenerational effects of ionizing radiation on tissues and on organisms level were clearly shown in animals. For the estimation of pathogenic role of radiation induced genomic instability in humans, particularly in children of exposed parents the parallel study of the same human cohorts using clinical parameters and various characteristic of genomic instability seems to be very important.

Child, Preschool↗
PubMed1991

An appreciation of posterior instability of the shoulder.

Fortunately, posterior instability of the shoulder is a relatively uncommon occurrence in the athlete. Acute traumatic posterior dislocations can be readily managed by conservative measures. Recurrent posterior subluxation, however, represents a more challenging problem for the orthopedic surgeon. As has been discussed, most patients with this disorder respond to nonsurgical treatment including physical therapy and modification of the offending activities. Should these modalities fail, operative treatment may be necessary. Careful assessment of the patient to rule out the associated presence of excessive ligamentous laxity or a voluntary component to the instability is mandatory. Pain is clearly the principal indicator for surgical treatment. Painless subluxation, either voluntary or involuntary, should first be treated conservatively. The surgical options discussed in this article range from simple soft-tissue repair to more complex osteotomies with combined capsular plication. It is important that the procedure be appropriate to the pathology. We do not believe that one technique alone can address all variants of posterior instability. Most instances of recurrent posterior subluxation represent unidirectional instability in patients with otherwise normal bony morphology. In these patients, a posterior capsulorrhaphy combined with appropriate immobilization should be effective. In select instances, when either excessive glenoid retroversion or deficiency is encountered, a glenoid osteotomy and posterior capsulorrhaphy have proved successful. This technique, more than any other, carries a number of potential technical pitfalls and should be employed cautiously. Multidirectional posterior instability, now a well-recognized entity, requires a different surgical approach--the capsular shift. Designed to address the inferior redundancy, as well as posterior laxity, this procedure is applicable to the multidirectional posterior subluxator. In conclusion, posterior instability of the athlete's shoulder is an increasingly recognized entity. Most instances are amenable to nonsurgical care. Should surgical treatment be necessary, optimal results may be achieved by careful attention to patient assessment, instability categorization, determination of the presence of ligamentous laxity, and appropriate surgical technique.

Humans↗
PubMed1983

Acute posterolateral rotatory instability of the knee.

We reviewed the clinical records and operative notes of seventeen consecutive patients who were treated by surgical repair for acute posterolateral rotatory instability in order to determine the diagnostic features of the instability and the effectiveness of our surgical repair in thirteen patients who returned for objective and subjective evaluation after a mean follow-up of 53.3 months. Sixteen of the seventeen knees had a positive external-rotation recurvatum test; fifteen, a positive adduction-stress test at 30 degrees of knee flexion; and twelve, a positive posterolateral-drawer test. Associated rotatory instabilities were found in ten of the seventeen knees, with anterolateral rotatory instability being the most frequent. Two patients had associated peroneal-nerve palsy. One or more components of the arcuate ligament complex were injured in all seventeen knees. None of the thirteen patients who were followed required subsequent reconstruction for any chronic instability. Of these thirteen, the results in 85 per cent were rated good subjectively and in 77 per cent, good objectively. Eighty-five per cent of these patients had returned to athletic activity at their preinjury level; the remaining 15 per cent did not participate in sports activities. A positive posterolateral-drawer test or external rotation recurvatum test, or both, was diagnostic of posterolateral rotatory instability. The adduction stress test at 30 degrees of knee flexion was usually positive, but was not diagnostic. Accurate diagnosis and treatment of posterolateral rotatory instability in the acute stage can result in subjectively and objectively acceptable knee function.

Adolescent↗
PubMed1994

[Carpal instability associated with fracture in distal radius].

Among 197 fractures in distal radius, 65 fractures were found accompanied with carpal instability, with an incidence of 32.9 percent. Six patterns of the instability were observed, in which dorsiflexion instability and scapholunate dissociation were predominant. The occurrence and patterns of instability were related to the types of the fractures, curve and palmar tilt angle of the distal radial articular surface. 64.9 percent of the instability was corrected during reduction of the fracture, but 35.1 percent remained. Compared with the fractures without carpal instability, functions of the wrists were worse in the fractures with the instability. The pathogenesis of these injuries and clinical significance of this study were discussed.

Adolescent↗
PubMed1994

Anatomy, biomechanics, and physical findings in posterolateral knee instability.

Posterolateral injury is often associated with additional ligamentous injury to the knee. Proper evaluation of these injuries requires a knowledge of the anatomy and biomechanics of the posterolateral corner. Biomechanical studies reveal that the popliteal tendon, the popliteofibular ligament, the arcuate ligament, and the LCL are the principal structures responsible for maintaining stability of the posterolateral corner. Knowledge of the biomechanics of the posterolateral corner provide insight into the clinical evaluation and treatment of posterolateral knee instability. Patients with acute and chronic posterolateral instability present with complaints of knee pain and instability of the knee in extension. Patients may also complain of dysthesias or motor weakness owing to associated peroneal nerve injury. Patients may also present with symptoms pertaining to associated ligamentous injury to the knee. Thorough examination is needed to document neurovascular status, and the presence of posterolateral and associated knee instability. Although many tests are used to document posterolateral knee instability, the authors prefer varus stress testing and the prone external rotation test. Accurate diagnosis of all knee ligament pathology will allow appropriate planning for the surgical treatment of isolated posterolateral knee instability and combined instability patterns.

Anterior Cruciate Ligament↗
PubMedDate not supplied

Surgical treatment of low back pain in spine instability.

Spinal instability is a loosely used term resulting from a variety of traumatic, developmental, neoplastic, hereditary, and degenerative insults to the axial skeleton. As defined by White and Panjabi, lumbar instability would imply the loss of the spine's ability, under physiological loads, to maintain its patterns of displacement so as to avoid neurologic deficits, incapacitating deformity, and intractable pain. Although from a strict engineering standpoint, the concept of load and deformation is valid, it is not at all known what type of movement or what magnitude of movement is responsible for low back pain. In light of these considerations, the author would define instability as either acute or chronic. Acute mechanical instability would result from those conditions such as fracture, tumor infiltration, infection, postlaminectomy, and certain congenital defects where a small change in loading or deformation could lead to permanent vertebral displacement with fixed deformity and/or neurologic damage. Chronic instability would result from those low back disorders that lead to progressive deformity over a period of years, often producing back pain from degenerative osteoarthritis, and central as well as foraminal stenosis. These disorders would include lumbar scoliosis, kyphosis, and spondylolisthesis, either isthmic or degenerative type. In those situations associated with more chronic instability, the relationship of low back pain is not always discernable even with provocative discography or magnetic resonance imaging. The surgical treatment of low back pain associated with these spinal instabilities depends on the etiology of the conditions defined. Acute traumatic injuries are best managed by posterior segmental instrumentation. At the level of the upper lumbar spine, a combined approach may be desirable to support anterior column deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1993

Classification and physical diagnosis of instability of the shoulder.

Recent clinical and basic science work has increased our knowledge of shoulder instability. Valuable information has been gained by cutting studies of the capsuloligamentous complex to clarify the biomechanics of instability. It is now clear that a significant overlap exists in the concepts of instability and impingement relating to anterior shoulder pain. These concepts have added new importance to organization and standardization when classifying and diagnosing shoulder instability. This manuscript presents an algorithmic approach to classification of shoulder girdle complaints that may be related to instability. This classification system is designed around the direction, degree, chronology, cause, and volition of instability. With accurate and detailed analysis of the historical presentation, most shoulder instability complaints can be classified using this approach. The physical examination also should proceed in an orderly fashion, including general impression of the musculoskeletal system, inspection, palpation, and range of motion of both the uninvolved and involved shoulder, neurologic examination, rotator cuff evaluation, and stability assessment. Stability assessment includes glenohumeral translation examination with apprehension and provocative testing. Management techniques are predicted on an accurate diagnosis. With a thorough and organized examination, the correct diagnosis can be achieved.

Adult↗
PubMed1995

Postfusion instability at the adjacent segments after rigid pedicle screw fixation for degenerative lumbar spinal disorders.

Sixty-five patients who underwent wide laminectomy, Cotrel-Dubousset instrumentation, and fusion for lumbar degenerative disorders were reviewed radiographically to investigate the incidence and contributing factors of the postfusion instability at the adjacent segments immediately above or below the level of fusion. Thirty-four were men and 31 were women. The mean age was 55.8 years. The average follow-up time was 39 months. Postfusion instability was studied at a total of 107 adjacent segments in 65 patients. The incidence of postfusion instability noted at final follow-up was 24.6% (15 of 61 patients). The incidence was significantly more often observed in the adjacent segments above the fusion than below the fusion, at rates of 25.5 and 2.6%, respectively. The most common instability was posterior translation (9 of 15 patients). Regarding contributing factors for instability at the adjacent segment above the fusion levels, the age of patients was the most significant factor. The incidence was 36.7% (11 of 30 patients) in older patients (> 55 years old) and 12% (3 of 25 patients) in younger patients (< 55 years old). In four patients with a preoperative of > 3 mm anterior translation, instability progressed further postoperatively. To prevent postoperative instability, attention must be paid especially above the fusion levels of the elderly and the preoperative minimal anterior translation.

Adult↗
PubMed2002

Instability on hospital discharge and the risk of adverse outcomes in patients with pneumonia.

BACKGROUND: Investigating claims that patients are being sent home from the hospital "quicker and sicker" requires a way of objectively measuring appropriateness of hospital discharge. OBJECTIVE: To define and validate a simple, usable measure of clinical stability on discharge for patients with community-acquired pneumonia. METHODS: Information on daily vital signs and clinical status was collected in a prospective, multicenter, observational cohort study. Unstable factors in the 24 hours prior to discharge were temperature greater than 37.8 degrees C, heart rate greater than 100/min, respiratory rate greater than 24/min, systolic blood pressure lower than 90 mm Hg, oxygen saturation lower than 90%, inability to maintain oral intake, and abnormal mental status. Outcomes were deaths, readmissions, and failure to return to usual activities within 30 days of discharge. RESULTS: Of the 680 patients, 19.1% left the hospital with 1 or more instabilities. Overall, 10.5% of patients with no instabilities on discharge died or were readmitted compared with 13.7% of those with 1 instability and 46.2% of those with 2 or more instabilities (P<.003). Instability on discharge (> or =1 unstable factor) was associated with higher risk-adjusted rates of death or readmission (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.8) and failure to return to usual activities (OR, 1.5; 95% CI, 1.0-2.4). Patients with 2 or more instabilities had a 5-fold greater risk-adjusted odds of death or readmission (OR, 5.4; 95% CI, 1.6-18.4). CONCLUSIONS: Instability on discharge is associated with adverse clinical outcomes. Pneumonia guidelines and pathways should include objective criteria for judging stability on discharge to ensure that efforts to shorten length of stay do not jeopardize patient safety.

Adolescent↗
PubMed1997

Microsatellite instability in sporadic mucinous colorectal carcinomas: relationship to clinico-pathological variables.

A series of 44 sporadic mucinous colorectal carcinomas was analysed for microsatellite instability; 30 consecutive sporadic non-mucinous colorectal cancers served as controls. Mucinous carcinomas showed microsatellite instability more frequently than non-mucinous cancers: 26/44 and 8/30, respectively (P = 0.005); the difference was higher for cancers with two or more microsatellite alterations: 12 of the 44 mucinous carcinomas versus one of the 30 non-mucinous carcinomas (P = 0.007). On comparing the clinico-pathological features of mucinous carcinomas with and without microsatellite instabilities, no differences were found with respect to the following variables; sex ratio, tumour localization, tumour size, peritumoural lymphocytic infiltration, Crohn's-like lymphoid reaction, peritumoural fibrosis, Dukes' stage, and relationship with adenoma. Mucinous cancers with DNA replication errors were characterized by three features: onset in younger patients (P < 0.05); exophytic gross shape (P = 0.03); and an expanding pattern of growth (P = 0.003). Of the 12 mucinous carcinomas with instability in two or more microsatellites, ten (83.3 per cent) exhibited an expanding pattern of growth, while mucinous cancers with instability in one microsatellite or without genomic instability showed no distinctive growth pattern. This study confirms the relationship between microsatellite instabilities and mucin production in colorectal carcinomas, but shows that replication error RER-positive and RER-negative mucinous cancers differ in few clinico-pathological features. These differences are only in part similar to those previously reported in RER-positive colorectal carcinomas. These data indicate that mucinous carcinoma of the large bowel could represent a histological subset separate from other histotypes.

Adenocarcinoma, Mucinous↗
PubMed2005

A substantial proportion of microsatellite-unstable colon tumors carry TP53 mutations while not showing chromosomal instability.

Chromosomal instability in colon tumors implies the presence of numerical and structural chromosome aberrations and is further characterized by the absence of microsatellite instability and the occurrence of KRAS and/or TP53 mutations. In a previous screening of 194 colon tumors for both microsatellite instability and TP53 mutation, we found 25 microsatellite-unstable tumors, in 9 (36%) of which, presumed to be chromosomally stable, there were TP53 mutations. This prompted us to investigate whether a TP53 mutation in these microsatellite-unstable tumors would be an indicator of chromosomal instability, that is, whether this would be a category of tumors showing both microsatellite and chromosomal instability. For chromosomal instability assessment, we performed array-comparative genomic hybridization analysis of tumor and control DNA extracted from formalin-fixed, paraffin-embedded stage III colon tumor specimens. The array consisted of 435 subtelomere-specific BACs. We compared all but one (whose DNA was of bad quality) of the microsatellite-unstable TP53 mutation-containing tumors (8) with a similarly sized group of microsatellite-unstable tumors without TP53 mutation (11). Microsatellite-unstable tumors with a TP53 mutation showed on average 0.9 aberrations (range 0-3) when assessed with this array system. Those without a TP53 mutation showed on average 0.7 aberrations (range 0-2). Thus, microsatellite-unstable tumors showed few chromosomal abnormalities regardless of TP53 mutation status. Because, in our study, the microsatellite-stable tumors had on average 3.4chromosomal abnormalities (range 0-7), a clear difference exists between microsatellite-unstable and -stable tumors. Because a substantial proportion of microsatellite-unstable colon tumors carry a TP53 mutation while showing relativelyfewchromosomal aberrations, a TP53 mutation in these tumors cannot be considered to be an indicator of chromosomal instability.

Chromosomes, Artificial, Bacterial↗
PubMed2002

Genomic instability measurement in the diagnosis of thyroid neoplasms.

BACKGROUND: Clinically palpable thyroid nodules are present in approximately 10% of the population, although only 5% to 7% of these nodules harbor malignancy. Fine-needle aspiration has become one of the central tools in the diagnostic armamentarium of the surgeon/endocrinologist. There is, however, up to a 30% indeterminate diagnostic rate associated with this technique, resulting in unnecessary surgical interventions for patients harboring benign disease. A second issue of clinical importance is the unreliability of predicting outcomes based either on histologic findings alone or in combination with clinical staging. To address these diagnostic and clinical shortcomings, we have used measurement of genomic instability as a diagnostic and prognostic indicator for thyroid neoplasms. METHODS: Genomic instability of thyroid tissue samples was determined by inter-(simple sequence repeat) PCR, microsatellite instability analysis, and fluorescence in situ hybridization (FISH) on thyroid neoplasms from 22 patients. RESULTS: Inter-(simple sequence repeat) PCR detected genomic instability with an index range 0% to 1.9% (mean, 0.56%) in patients with benign disease, whereas in patients with malignant histologic findings the values ranged from 0% to 6.6% (mean, 2.9%). This difference between benign and malignant values was statistically significant (p =.004). There was no demonstrable microsatellite instability or loss of heterozygosity for six markers examined in this group. Losses of chromosomes 17 and X in benign disease and gains of chromosomes 7, 12, 17, and X in Hurthle cell carcinoma were observed, although not at a significant rate. CONCLUSIONS: Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability.

Adolescent↗
PubMed2004

Different types of microsatellite instability in ovarian carcinoma.

Microsatellite instability at mono- and dinucleotide repeats is the hallmark of the hereditary non-polyposis cancer syndrome (HNPCC) and is related to deficient DNA mismatch repair. In contrast, a distinct form of microsatellite instability at selective tetranucleotide repeats (EMAST or elevated microsatellite alterations at selected tetranucleotides) was described in several non-HNPCC cancer types. EMAST is probably unrelated to mismatch repair defects. We investigated the frequency of microsatellite instability at mononucleotide, dinucleotide and tetranucleotide repeats in a series of 75 ovarian carcinomas (53 serous and 22 non-serous). Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel and 6 tetranucleotide markers, which have been reported as frequently unstable in the literature. High frequency of microsatellite instability (MSI-H) at mono- and dinucleotide repeats was observed in 9% and a low frequency (MSI-L) in 21% of serous carcinomas. MSI-H was detected in 4% and MSI-L in 18% of non-serous carcinomas. Nine percent of serous carcinomas showed instability at multiple and 9% at single tetranucleotide loci. All non-serous carcinomas were stable at tetranucleotide loci. In summary, EMAST (e.g., tumors with tetranucleotide instability without concomitant MSI-H) was observed in 13% of ovarian serous carcinomas. All EMAST positive tumors were of advanced stage. We conclude that EMAST occurs as a distinct form of microsatellite instability in ovarian cancer. EMAST seems to be particularly frequent in advanced serous carcinomas. Its clinical significance needs to be investigated.

Carcinoma↗
PubMed1995

Microsatellite instability and pathological aspects of breast cancer.

Genomic instability plays a key role in hereditary nonpolyposis colorectal cancer and in a significant sub-set of non-hereditary colorectal tumors. Recent evidence suggests that microsatellite instability also occurs in various sub-sets of common, non-hereditary forms of extra-colorectal carcinoma. To investigate the role of microsatellite instability in breast cancer, and to correlate this type of alteration with clinico-pathological characteristics, including tumor proliferative activity, we analyzed the status of 8 different microsatellite loci in 28 cases of primary mammary carcinoma. For this purpose, microsatellite banding patterns were compared in paired breast-cancer/peripheral-blood DNA samples. Microsatellite instability was observed in 6/28 (21%) of the cases. Four of the 6 tumors had low proliferative activity, one had high proliferative activity, and in one case proliferative activity values were not available. All chromosomal loci investigated demonstrated microsatellite instability in one or more representative tumors of the series. Shifts in length larger than 2 bp were the most frequent change. Microsatellite instability significantly correlated with the lobular histotype, and with lymph-node involvement. A trend was also observed associating microsatellite instability and large tumor size.

Adult↗
PubMed1995

Microsatellite instability in oral cancer.

Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors.

Adult↗