Biomedical subjects

M J Merino

Publications and source records attributed to M J Merino.

At least 37 records · Page 2Linked to original sources

PubMed1999

Incidence of loss of heterozygosity at p53 and BRCA1 loci in serous surface carcinoma.

Serous surface carcinoma (SSC) is a neoplasm histologically indistinguishable from typical serous carcinomas that arise from the ovary but has a distinct clinical presentation. It is characterized by widespread peritoneal dissemination at presentation, but the ovaries are grossly normal in size and shape. If the carcinoma involves the ovaries microscopically, the tumor is confined to the surface or is minimally invasive. The recognition of this entity is important, because in some studies it appears to have a poorer prognosis than stage-matched serous cancers of the ovary. Loss of heterozygosity (LOH) of the p53 (17p) and BRCA1 (17q) tumor suppressor genes has been frequently identified in sporadic ovarian carcinomas. Although 17p LOH is correlated with common p53 gene mutations, inactivating mutations of the BRCA1 gene are uncommon in sporadic ovarian cases. In contrast, germline BRCA1 mutations are responsible for some hereditary forms of ovarian cancer, where it has been suggested that germline BRCA1 mutations confer a more favorable prognosis. In this study, 12 sporadic SSC were assessed for the presence of allelic deletions on the p53 and BRCA1 gene loci. DNA from both tumor and normal cells was obtained for LOH studies using tissue microdissection. Polymerase chain reaction (PCR) amplification was performed with the polymorphic DNA markers TP53 (17p13.1/p53 gene) and D17S579 (17q/BRCA1 gene). LOH in the p53 and BRCA1 loci was detected in 62.5% and 66.6% of the cases, respectively. In 50% of tumors informative for both markers, it is possible that an entire chromosome may be lost. In conclusion, we have shown that LOH of the p53 and BRCA1 loci is a frequent event in sporadic SSC, similar to what has been described in the usual form of serous ovarian carcinoma. Mutational analysis will be necessary to determine the exact role of these genes in this group of tumors.

Chromosomes, Human, Pair 17↗

PubMed1999

LOH at the APC/MCC gene (5Q21) is frequent in early stages of non-small cell lung cancer.

Lung cancer is the leading cause of death in both women and men in the United States and many European countries. Molecular cytogenetic and LOH analyses of non-small cell lung cancer have shown somatic genetic alterations in a variety of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q and 17p. Allelic deletions of the known tumor suppressor gene APC at 5q21 are frequently observed in advanced stages of lung cancer and have been correlated with poor prognosis in previous reports. We investigated 33 cases of NSCL for LOH at 5q21: 22 squamous cell and 11 adenocarcinomas. Normal and tumor cells were microdissected from paraffin embedded tissues and PCR amplification was performed utilising the specific markers D5S299 and D5S346 at 5q21 and PYGM at 11q13, respectively. Clinicopathological data, survival and recurrence rates were obtained in all cases. We detected LOH at 5q21 in 4/9 (44%) informative adenocarcinomas and in 13/16 (81%) informative SCC. LOH was frequent in early stages (12/15 stage I cases) and did not correlate with recurrence or poor survival. Our results show that LOH at 5q21 is more frequent in squamous cell carcinomas than in adenocarcinomas, is frequent in early stages of the disease, and does not have prognostic significance.

Adenocarcinoma↗

PubMed1999

The use of microsatellite instability in the distinction between synchronous endometrial and colonic adenocarcinomas.

The association of endometrial carcinoma with other gynecologic neoplasms, especially ovarian and fallopian tube carcinoma, has been well documented and is usually interpreted as a result of a field defect. Sporadic synchronous primary carcinomas occurring in the endometrium and colon are extremely rare, especially in the absence of the familial genetic abnormalities seen in hereditary nonpolyposis colorectal carcinoma (HNPCC) syndrome, and may present a diagnostic dilemma. Two cases of synchronous adenocarcinomas of the endometrium and colon were studied for genetic abnormalities and differences to test for the presence of two primary tumors. Primary tumors, metastases, and normal tissues were microdissected from formalin-fixed, paraffin-embedded tissues. PCR amplification was performed for microsatellite DNA markers on chromosome 17q and 11q13. The colonic tumors were moderately and poorly differentiated, invasive, nonmucinous adenocarcinomas, whereas one uterine tumor was endometrioid adenocarcinoma and the other was papillary serous carcinoma. Although microsatellite instability, as evidenced by changes in the lengths of the amplified PCR products, was detected at 17q and 11q13 loci in the uterine and colonic neoplasms, the patterns of instability differed between the two primary tumor sites. Moreover, the lymph node metastasis in one colonic tumor had genetic alterations that differed from that of the primary tumor. In both patients, the molecular studies suggested the presence of two synchronous primary tumors. Molecular techniques may assist in distinguishing two separate primaries by determining the contraction and expansion of microsatellite regions in DNA obtained by microdissection from the primary tumors and associated metastases.

Adenocarcinoma↗

PubMed1999

Infiltrating micropapillary carcinoma of the breast.

Infiltrating micropapillary carcinoma of the breast is a recently described and poorly recognized aggressive variant of infiltrating ductal carcinoma for which the clinical significance and role of prognostic markers are not fully described. In 14 cases of infiltrating micropapillary carcinoma, we studied histologic characteristics; immunohistochemical expression of c-erbB-2, p53, and MIB-1; hormonal expression of these tumors; and genetic alterations on the p53 locus. We correlated these results with clinical outcome. Patient ages ranged from 37 to 58 years (mean, 50 yr). Nine patients presented with a palpable tumor, one with an axillary mass. Three patients had abnormal mammograms. Five patients (36%) presented with Stage II disease, eight (57%) with Stage III, and one (7%) with Stage IV. The tumors were a modified Bloom-Richardson Grade II in nine cases (64%) and Grade III in 5 (36%). Mitoses ranged from 1 to 12 per 10 high power fields. Necrosis was uniformly absent. Psammoma bodies were present in 9 cases (64%) and lymphatic invasion in 10 (71%). In all of the cases, c-erbB-2 was identified immunohistochemically, and MIB-I was positive, staining 30 to 60% of the tumor cells. The cells were immunoreactive for p53 in six (75%) of eight cases, and, when present, stained 20 to 50% of the tumor cells. Loss of heterozygosity on locus 17p13.1 (p53) was identified in 4 of 5 informative samples. Molecular and immunohistochemical analyses had an 80% concordance. Follow-up was available in 11 patients, of whom 9 had recurrence in the skin and chest wall (average time of recurrence, 24 mo). Recognition of this distinctive and aggressive variant of infiltrating carcinoma is important because of its unfavorable prognosis and specific pattern of local recurrence. Its aggressive nature is supported by its advanced stage at presentation and expression of unfavorable prognostic markers.

Adult↗

PubMed1999

Breast cancer in young women: clinicopathologic correlation.

It has been suggested that early-onset breast carcinomas may be different from those that occur in older women. The clinicopathologic characteristics of 191 young female patients (under 40 years of age) diagnosed with breast carcinoma (BC) were studied. Clinical history, staging, treatment and outcome were reviewed. Histology was assessed for tumor subtypes, invasive and in situ components, nuclear and histologic grades and lymph node status. Adjacent nontumoral breast tissue was evaluated. Clinically, 11 patients were stage 0, 21 stage I, 94 stage II, 38 stage III, 6 stage IV, and in 21 no information was obtained. Sixty five percent of patients had positive lymph nodes at diagnosis; 102 patients (54%) relapsed at a median of 29 months after diagnosis. Histologically, 180 cases were infiltrating BC, 150 ductal (83%), 19 lobular (11%) and 11 of special types (6%); 11 cases were ductal carcinoma in situ. We found no cases of medullary carcinoma. High nuclear grade and vascular invasions were frequent (68% and 67%, respectively) even in patients who remained disease-free at least 5 years after diagnosis (61% and 60%, respectively). Our study demonstrates that the histologic types of early-onset breast cancer are not different from other BC. However, BC in young women is often associated with histologic features of high-grade malignancy even in patients with better survival. Our results suggest that BCs in young women are different from those that occur in older women.

Adult↗

PubMed1999

Histopathology and molecular genetics of renal tumors toward unification of a classification system.

PURPOSE: We characterize the genetic abnormalities associated with pathological subtypes of renal tumors, which may help diagnosis or prognostication. MATERIALS AND METHODS: A comprehensive literature review of genetic abnormalities associated with different renal tumor subtypes was performed. RESULTS: Studies of sporadic and hereditary forms suggest that abnormalities in the von Hippel-Lindau and met genes are the earliest changes in conventional (clear cell) and papillary basophilic renal cancers, respectively. Renal oncocytoma and chromophobe carcinoma have common genetic abnormalities, suggesting a relationship. A similar finding has been observed between papillary adenoma and papillary basophilic renal cancer. CONCLUSIONS: These findings suggest that molecular diagnostic testing will help determine histopathological diagnosis, identify tumor types with similar genetic abnormalities suggesting a common origin and indicate potential prognostic markers for future study.

Humans↗

PubMed1998

Allelic loss on chromosome 22q in epithelioid sarcomas.

Epithelioid sarcomas are soft tissue tumors with an indolent, but potentially aggressive, clinical behavior. Distinction from other benign and malignant entities may be a diagnostic dilemma. In this study, we evaluate the presence of loss of heterozygosity (LOH) of chromosome 22q in tumor DNA from 13 epithelioid sarcomas, four epithelioid angiosarcomas, and two epithelioid hemangioendotheliomas, and investigate its possible role in diagnosis. LOH was detected in 6 of 10 (60%) of the informative epithelioid sarcomas. No allele loss was detected in the informative vascular tumors, three angiosarcomas, and two hemangioendotheliomas. Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors. Our data suggest that a region of chromosome 22q may be the locus of a tumor suppressor gene involved in the tumorigenesis of these neoplasms. Genetic alterations of yet-unknown tumor suppressor genes in this region, or even the NF2 tumor suppressor gene, may play a role in epithelioid sarcomas tumorigenesis. The fact that LOH was only detected in epithelioid sarcomas and not in the vascular tumors studied suggests a possible role for this marker in diagnosis.

Adolescent↗

PubMed1998

The histological spectrum of hemangiopericytoma: application of immunohistochemical analysis including proliferative markers to facilitate diagnosis and predict prognosis.

Hemangiopericytoma (HPC) is an uncommon vascular neoplasm thought to be derived from pericytes. Prediction of patient outcome is difficult based what is currently known about these tumors and histological parameters alone. We compiled 27 cases of HPC and evaluated the spectrum of histological features to investigate whether there was any correlation between histology, immunostaining, prognostic markers, and patient outcome. The following parameters were evaluated: vasculature, histological pattern (solid, myxoid, trabecular, alveolar), degree of cellular pleomorphism, necrosis, mitoses, and giant cell content. Immunohistochemistry was performed to determine the reactivity for CD 31, CD34, vimentin, actin, cytokeratin, S100, actin, and SMA. Proliferative rate was analyzed using antibodies to PCNA and MIB1. Patient's age ranged from 8 months to 75 years (mean, 35; median, 31). Twenty of 27 cases were located in the extremities. The tumors were grossly described as lobulated and well circumscribed (n=12) and nonencapsulated (n=15). By histology, the characteristic ramifying or staghorn vasculature pattern was seen in all cases. A solid histological pattern was mixed with an alveolar pattern in three cases, trabecular pattern in six cases, and myxoid pattern in two cases. Tumor cells were uniform, polygonal to spindle-shaped, often with vesicular nuclei. Tumor giant cells were present in 9 of 27 cases; necrosis, in 11 of 27. Mitoses ranged from 0 to 14 per 10 high-power fields (HPF). Cellular pleomorphism was 1+ in nine cases, 2+ in 12 cases, and 3+ in six cases. Immunohistochemistry showed reactivity for CD34 and vimentin in all cases. Actin was focally positive in one case, and SMA was focally positive in another. CD 31, cytokeratin, and S100 were uniformly nonreactive. Proliferative index measured by PCNA and MIBI ranged between less than 1% and 40% of tumor cells. Follow-up was available in 22 cases and ranged from 1 year to 15 years. Seven patients had metastases, and two recurred locally. Thirteen patients had no evidence of disease at last checkup. Parameters associated with recurrences or metastases include a trabecular pattern, the presence of necrosis, mitoses, vascular invasion, and cellular pleomorphism. Features associated with an aggressive biological behavior can be identified histologically. There was some, but not total, correlation between proliferative markers and tumor aggressiveness.

Adolescent↗

PubMed1998

Utilization of molecular genetics in the differentiation between adrenal cortical adenomas and carcinomas.

Distinction between benign adrenal cortical proliferative lesions and adrenal cortical carcinoma has been approached by a combination of histological, immunohistochemical, and macroscopical parameters. Modern imaging studies allow detection of small adrenal cortical lesions that may be incorrectly diagnosed. Differentiation between benign and malignant tumors of the adrenal cortex was attempted by microdissection of nine cases of adrenal cortical hyperplasia, 10 cortical adenomas, and 18 adrenal cortical carcinomas with subsequent polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of five microsatellites of putative tumor suppressor gene loci: p53 gene (17p), the neuroblastoma candidate gene (1p), the p16 gene (9p), the von Hippel Lindau gene (3p), and the retinoblastoma gene (13q). None of the hyperplastic lesions or cortical adenomas showed LOH of any of the gene markers used. Conversely, genetic changes were observed in 61% (11 of 18) of the cases of carcinoma. Forty-four percent of the lesions showed LOH for p53 (7 of 16). LOH of 1p, 3p, and 9p were seen in 22%, 22%, and 26%, respectively. LOH of the retinoblastoma gene was seen in 80% or four of five of the informative cases studied. We conclude that LOH studies may be used to distinguish malignant from nonmalignant adrenal cortical proliferations. Relative infrequency of LOH in 3p may furthermore help to differentiate adrenal lesions from clear cell carcinomas of the kidney.

Adenoma↗

PubMed1998

C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: immunohistochemical analysis and clinicopathologic correlation.

We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to 50. Clinicopathological criteria including clinical stage, hormone receptor status, histological types, histological grades, and lymph node status, were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed. Immunohistochemical findings were assessed semiquantitatively. Correlation between clinicopathological criteria, survival data, and immunohistochemical findings have been made. Patients aged younger than 35 years with stage I to II disease had a shorter DFS (P = .03) than older patients. However, no other clinicopathological finding was associated with age. Neither was there association between age and c-erbB-2, p53, or nm23 patterns of expression. p53 positivity was associated with high histological grade (P = .003) and with progesterone receptor negativity (P = .045). Nm23 nuclear positivity was associated with early clinical stages (P = .011) and with absence of axillary lymph node metastasis (P = .007). p53 and c-erbB-2 overexpression were associated with shorter OS while nm23 nuclear positivity was associated with longer OS in univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or nm23 were potentially important prognostic factors in women aged 35 years or younger while p53 was associated with prognosis in women aged 36 to 50. Cox model analysis indicated that c-erbB-2 alone was associated with prognosis in women 35 years and younger, whereas p53 alone was associated with prognosis in 36- to 50-year-old women. These results suggest that breast cancer in the youngest women has some biological specificity.

Adult↗

PubMed1998

Comparison of genetic alterations in colonic adenoma and ulcerative colitis-associated dysplasia and carcinoma.

Carcinoma is an important complication of ulcerative colitis (UC) and develops from dysplastic precursor lesions. Genetic changes involved in the malignant transformation have not been fully characterized. We studied 19 cases of UC with high-grade dysplasia (HGD) and eight samples of associated carcinoma (CA). Microdissection of normal epithelium, epithelium at the site of chronic inflammation, HGD, and CA was performed. Polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of the following polymorphic microsatellites of putative tumor suppressor gene loci was done: APC (5q), DCC (18q), p16 (9p), p53 (17p), and 8p12. To compare genetic alterations, 22 typical adenomas of the colon were studied with the markers for APC and pl6 gene loci. The results indicated that LOH of p16 and p53 were present in nondysplastic epithelium, HGD, and CA. However, the LOH in nondysplastic epithelium was detected in some associated HGD, but not all. Whereas LOH of p16 was present in 7 of 14 cases of HGD (50%), it was noted in only 1 of 22 adenomas (5.0%). LOH in the APC and DCC gene loci in UC was noted in HGD with associated CA, but LOH of APC was not present either in cases of nondysplastic epithelium or in HGD alone. Conversely, LOH in APC was present in 4 of 19 colonic adenomas. We conclude that LOH of p53 and p16 in nondysplastic epithelium may be associated with chronic reparative processes. These changes may lead to susceptibility to further genetic damage involving the APC and DCC gene loci in the development of dysplasia and progression of CA in UC. The low frequency of LOH in the p16 gene (9p) in adenomas compared with dysplasia in UC combined with infrequent LOH in APC gene loci in cases of pure dysplasia in UC may support this combination of markers as a clinical test for the differentiation of polypoid dysplasia from adenomas in UC.

Adenoma↗

PubMed1998

Histopathology and molecular biology of ovarian epithelial tumors.

Carcinogenesis in the ovary presents special features related to that organ. First, the preinvasive or even invasive lesions are difficult to detect, which explains why most cases are diagnosed at an advanced stage. Second, the group of tumors of low malignant potential (borderline tumors) are still a controversial category of ovarian lesions. Finally, familial ovarian tumors represent an interesting hereditary model of carcinogenesis at the molecular level. Flow cytometry and immunohistochemistry for proliferative markers or oncogenes provide important prognostic information in patients with ovarian tumors. Molecular data, such as loss of heterozygosity at specific genetic loci, also have been correlated with prognosis. Clonality studies in patients with multiple ovarian/pelvian lesions analyzing chromosome X inactivation patterns and genetic deletions or mutations have contributed to the understanding of the origin of these lesions. New technologies to study gene expression patterns, such as cDNA library construction and DNA microarray technologies, are being applied to study histologic phases of tumor progression, such as normal, preinvasive, and tumor tissues. It is hoped that these studies will contribute important information not only for a better understanding of the process of carcinogenesis, but also for assessing the biology and behavior of individual tumors, determining patient prognosis, and eventually influencing therapy.

Female↗

PubMed1998

Male adnexal tumour of probable Wolffian origin occurring in a seminal vesicle.

AIMS: Adnexal tumours of probable Wolffian origin are rare low-grade malignant neoplasms that have been previously described in the broad ligament, ovaries and retroperitoneum of females. All are characterized by small, bland epithelial cells growing in a diffuse, trabecular, or tubular pattern. The majority of the cases reported have pursued a benign clinical course. However, recurrences and distant metastases have been described. We present a case of a male adnexal tumour of probable Wolffian origin occurring in the left seminal vesicle of a 29-year-old man with 23 years of follow-up. RESULTS: The diagnosis is supported by immunohistochemical and electron microscopic findings: The tumour cells were immunoreactive for cytokeratin and vimentin while smooth muscle antigen and S100 protein were uniformly negative. By electron microscopy cells were arranged in an acinar pattern and surrounded flocculent, electron-dense material. Individual cells contained numerous dense bodies and free ribrosomes. The patient had recurrences at 14 and 23 years after initial diagnosis. CONCLUSION: This is the first report of this entity in a male. The literature on this unusual tumour is reviewed and the clinicopathological, immunohistochemical and ultrastructural features are described. The differential diagnosis of this seemingly indolent tumour is discussed with genitourinary tumours having a more aggressive clinical course.

Adnexal Diseases↗

PubMed1998

Genetic changes associated with primary Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a malignant tumor of the skin with a well-established neuroendocrine phenotype but an unknown histogenetic origin. Cytogenetic and molecular studies have shown evidence for genetic changes on the distal portion of chromosome 1p in different tumors with well-established neuroendocrine origins, specifically neuroblastomas, malignant melanomas, and pheochromocytomas. Involvement of chromosome 1 in MCC recently has been demonstrated by cytogenetic analysis and analysis of loss of heterozygosity (LOH) in metastatic tumor tissue. We performed analysis of LOH of the distal portion of chromosome 1p in paraffin material of 10 primary MCCs after tissue microdissection, using the polymorphic markers D1S160, D1S243, D1S468, D1S1646, and D1S1598. Seven of 10 analyzed MCCs shared a distal deletion involving 1p35-36. None of the cases showed 1p involvement proximal to 1p35. The findings are similar to those described for malignant melanoma, pheochromocytoma, and neuroblastoma, tumors known to originate from neural crest cells. In conjunction with previous cytogenetic data, we conclude that Merkel cell carcinogenesis shares pathogenetic mechanisms with other neoplasms of neural crest derivation.

Aged↗

PubMed1998

Tumor recurrence in stage I ovarian serous neoplasms of low malignant potential.

Eleven patients treated at the University of Texas M. D. Anderson Cancer Center for recurrent disease after resection of a stage I ovarian serous neoplasm of low malignant potential (SNLMP) are reported. At the time of diagnosis, the age of the patients ranged from 26 to 43 years (mean 33). Seven patients had stage IB tumors and 4 had stage IA tumors. All patients were treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The size of the ovarian tumors ranged from 4 to 15 cm in maximum dimension. Stromal microinvasion was seen in 2 cases, and foci of endosalpingiosis were seen in the peritoneum in 8 cases. Nine patients were treated with radiotherapy and 2 with chemotherapy. The time to recurrent disease ranged from 7 to 39 years (mean 16). Eight tumors recurred in the pelvis or abdomen, 2 in the neck with subsequent abdominal involvement, and 1 in the pleura without abdominal or pelvic involvement. In 10 cases, the recurrent tumors were serous carcinoma, and in 1 case it was a SNLMP. Recurrences were treated with chemotherapy in 10 cases and with hormones in 1 case. Seven patients died of progressive serous carcinoma 2 to 5 years after the recurrence. One patient died of leukemia with recurrent ovarian tumor 10 years after the recurrence was detected. Two patients are alive with progressive disease 1 and 7 years after the recurrence, and 1 patient whose disease recurred as a SNLMP is alive with no evidence of disease 9 years after the recurrence. These 11 patients were compared with 16 patients who had stage I ovarian SNLMPs that did not recur after a minimum follow-up of 15 years. There was no difference in the age of the patients, gravidity, size of the tumors, or several microscopic parameters, including degree of epithelial proliferation, number of mitoses, and nuclear atypia. Microinvasion was found in one case. The only significant difference between the two groups was the low frequency of endosalpingiosis in the cases that had no disease recurrences (12.5% versus 72.7%). In summary, we found no clinical or pathologic features that can unequivocally predict the recurrence of stage I ovarian SNLMPs. Because of the long interval to recurrence, the fact that the recurrent tumors in 10 of 11 patients were serous carcinomas, and the result of the X-chromosome inactivation in one case, the recurrent tumors could represent independent primaries or a slow progression of one clone present in the SNLMPs.

Adult↗

PubMed1998

Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.

PURPOSE: This randomized, prospective study assesses the impact of postoperative external-beam radiation therapy on local recurrence (LR), overall survival (OS), and quality of life after limb-sparing resection of extremity sarcomas. PATIENTS AND METHODS: Patients with extremity tumors and a limb-sparing surgical option were randomized to receive or not receive postoperative adjuvant external-beam radiotherapy. Patients with high-grade sarcomas received postoperative adjuvant chemotherapy whereas patients with low-grade sarcomas or locally aggressive nonmalignant tumors were randomized after surgery alone. RESULTS: Ninety-one patients with high-grade lesions were randomized; 47 to receive radiotherapy (XRT) and 44 to not receive XRT. With a median follow-up of 9.6 years, a highly significant decrease (P2 = .0028) in the probability of LR was seen with radiation, but no difference in OS was shown. Of 50 patients with low-grade lesions (24 randomized to resection alone and 26 to resection and postoperative XRT), there was also a lower probability of LR (P2 = .016) in patients receiving XRT, again, without a difference in OS. A concurrent quality-of-life study showed that extremity radiotherapy resulted in significantly worse limb strength, edema, and range of motion, but these deficits were often transient and had few measurable effects on activities of daily life or global quality of life. CONCLUSION: This study indicates that although postoperative external-beam radiotherapy is highly effective in preventing LRs, selected patients with extremity soft tissue sarcoma who have a low risk of LR may not require adjuvant XRT after limb-sparing surgery (LSS).

Extremities↗

PubMed1998

A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor.

The development of prevention strategies for breast cancer will require a molecular map of carcinogenesis. We have investigated gene expression patterns in premalignant and early carcinomatous human breast lesions that confer to the patient varying risks for developing invasive breast cancer. The relative expression levels of one of the retinoid receptors, retinoid X receptor (RXR), was determined by in situ hybridization to 58 biopsy specimens; RXR mRNA grain density over each lesion was compared to that over the normal ductal/lobular units in each section. Overexpression of RXR mRNA was observed in 66% of noncomedo ductal carcinoma in situ (DCIS), which confer a >8-fold increase in breast cancer risk, and 88% of comedo DCIS lesions, which are associated with a yet higher risk. In contrast, only 8% of lesions that confer little or no increase in breast cancer risk overexpressed RXR mRNA (P = 0.0008). Limited in situ hybridization data using retinoic acid receptor (RAR) riboprobes showed overexpression of RAR alpha, but not RAR beta or -gamma, in only a modest percentage (36%) of cases, suggesting that all members of the retinoid receptor superfamily are not similarly regulated. Immunohistochemistry performed on 52 DCIS specimens for alpha, beta, and gamma isoforms of RXR confirmed its overexpression at the protein level and implicate RXR alpha as the predominant overexpressed form. The data indicate that RXR overexpression is associated with an increased risk for the development of invasive breast cancer in human breast lesions and suggest the hypothesis that it is causally involved in breast oncogenesis. The implications for retinoid chemoprevention are discussed.

Biomarkers, Tumor↗

PubMed1998

Lymphoepitheliomalike carcinoma: an unusual variant of endometrial cancer. A report of two cases.

Two undifferentiated carcinomas of the endometrium with a prominent inflammatory reaction that were morphologically similar to nasopharyngeal cancers occurred in two patients who had postmenopausal bleeding. Tumor cells in both patients were large with indistinct cytoplasmic borders, vesicular nuclei, and prominent nucleoli, were arranged in sheets, in groups, or singly, and surrounded by an intense inflammatory component of lymphocytes, plasma cells, and karyorrhectic debris. Tumor cells were keratin (AE1/EA3) and epithelial membrane antigen (EMA) positive and leukocyte common antigen (LCA) negative. All three methods used for the detection of Epstein Barr virus (EBV) infection were negative. The first patient (International Federation of Gynecology and Obstetrics [FIGO] stage IVB) received chemotherapy and is alive and free of disease 9 months after diagnosis. The second patient (FIGO stage IIIC) received radiation therapy and chemotherapy 6 months after evidence of extensive retroperitoneal disease and died of disease 1 year after diagnosis. Tumors with these histologic features have been designated as lymphoepitheliomalike carcinomas (LELC) when they occur outside the nasopharynx. LELC can occur in the endometrium and, in this location, may not be associated with EBV infection.

Aged↗