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Biomedical subjects

M J Merino

Publications and source records attributed to M J Merino.

At least 19 recordsLinked to original sources
PubMed2006

Fibrous Histiocytoma-like Spindle-Cell Proliferation in the Nipple After Body-Piercing.

We report the case of a 19-year-old pregnant woman who presented with a nipple tumor. The lesion consisted in a spindle-cell proliferation with histologic features similar to those of fibrous histiocytoma, with a highly vascularized stroma. Although it showed low mitotic activity, scattered marked atypical cells with prominent nucleoli were identified, thus raising concern about the benign nature of the tumor. Immunohistochemical evaluation revealed that the spindle cells were diffusely positive for vimentin, focally positive for CD68, and negative for all the other tested antibodies. The patient had a total excision of the lesion and she is free of disease after 30 months. To our knowledge this is the first reported case of a lesion of this type in the nipple after body-piercing.

Adult↗
PubMed2005

Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC; OMIM 605839) is the predisposition to develop smooth muscle tumours of the skin and uterus and/or renal cancer and is associated with mutations in the fumarate hydratase gene (FH). Here we characterise the clinical and genetic features of 21 new families and present the first report of two African-American families with HLRCC. METHODS: Using direct sequencing analysis we identified FH germline mutations in 100% (21/21) of new families with HLRCC. RESULTS: We identified 14 germline FH mutations (10 missense, one insertion, two nonsense, and one splice site) located along the entire length of the coding region. Nine of these were novel, with six missense (L89S, R117G, R190C, A342D, S376P, Q396P), one nonsense (S102X), one insertion (111insA), and one splice site (138+1G>C) mutation. Four unrelated families had the R58X mutation and five unrelated families the R190H mutation. Of families with HLRCC, 62% (13/21) had renal cancer and 76% (16/21) cutaneous leiomyomas. Of women FH mutation carriers from 16 families, 100% (22/22) had uterine fibroids. Our study shows that expression of cutaneous manifestations in HLRCC ranges from absent to mild to severe cutaneous leiomyomas. FH mutations were associated with a spectrum of renal tumours. No genotype-phenotype correlations were identified. CONCLUSIONS: In combination with our previous report, we identify 31 different germline FH mutations in 56 families with HLRCC (20 missense, eight frameshifts, two nonsense, and one splice site). Our FH mutation detection rate is 93% (52/56) in families suspected of HLRCC.

Black or African American↗
PubMed2001

Detection of loss of heterozygosity at chromosome 3p25-26 in primary and metastatic ovarian clear-cell carcinoma: utilization of microdissection and polymerase chain reaction in archival tissues.

Loss of heterozygosity (LOH) at the 3p region is found in up to 50% of epithelial ovarian neoplasms. The von Hippel-Lindau (VHL) gene at the 3p25 locus is one of the tumor-suppressor genes located at 3p. The role, if any, of the VHL gene locus is not clear in ovarian carcinogenesis. We analyzed primary and metastatic ovarian clear-cell carcinomas (OCCC) for LOH at 3p25 to determine its frequency and its diagnostic utility as an adjunctive tool in the differential diagnosis of metastatic clear-cell carcinomas. Microdissection followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification, using two polymorphic markers flanking the VHL gene locus, was done on archival histology and cytology samples from 9 patients with metastatic OCCC. Of the informative cases, 43% of the metastatic and 50% of the primary OCCC showed LOH. LOH at the VHL gene locus is not uncommon in clear-cell ovarian carcinoma. LOH at 3p25 in cytologic specimens may be a valuable adjunct in the diagnosis of OCCC metastasis in cytologically equivocal cases. OCCC should enter the differential in clear-cell carcinomas of unknown primary that show LOH at 3p25. Published 2001 Wiley-Liss, Inc.

Adenocarcinoma, Clear Cell↗
PubMed2001

3p21, 5q21, and 9p21 allelic deletions are frequently found in normal bronchial cells adjacent to non-small-cell lung cancer, while they are unusual in patients with no evidence of malignancy.

Molecular cytogenetic and loss of heterozygosity (LOH) analyses of non-small-cell lung cancer (NSCLC) have shown frequent allelic deletions in a variety of chromosomes, such as 1p, 3p, 5q, 8p, 9p, 11p, 11q, and 17p. Allelic loss at 3p21, 9p21, and 5q21 has also been reported in premalignant epithelial lesions of the bronchus and in normal bronchial cells. These findings suggest that a tissue field of somatic genetic alterations precedes the histopathological phenotypic changes of carcinoma. LOH at chromosomal regions 3p21, 5q21, 9p21, and 17p (TP53) was looked for in the peritumoural normal bronchial cells from 30 archival surgically resected tumours. Microdissected normal bronchial cells from 20 benign cytological smears were also added to the study. Matched populations of lymphocytes, tumour cells, and normal bronchial cells adjacent to the tumour were microdissected from paraffin-embedded tissues, while matched populations of normal bronchial cells and inflammatory cells were microdissected from benign cytological smears (bronchial brushings). Polymerase chain reaction (PCR) amplification was performed utilizing the specific markers D5S346, D3S1300, D9S157, D9S171, and TP53. Within the NSCLC tumour cells, LOH was more frequently found at the 5q21 locus (72% of the informative cases), the 3p21 locus (47%), 9p21 (48%), and 17p (33%). Within the peritumoural normal bronchial cells, LOH at 5q21 was found in 37.5% of the cases, 22% showed LOH at 3p21, 27% at 9p21, and 13% at 17p (TP53). LOH was also detected in one case, in normal bronchial cells obtained from cytological smears at one locus (5q21). In conclusion, normal bronchial mucosa adjacent to NSCLC has frequent allelic losses at 3p21, 5q21, and 9p21, while LOH at these loci is unusual in normal bronchial cells obtained from cytological smears from patients with no evidence of malignancy. LOH at these loci may be present before the onset of the malignant growth. LOH studies may supplement the histopathological evaluation of bronchial cells to detect genotypic alterations in both cytological and biopsy specimens.

Adult↗
PubMed2001

Pigmented renal clear cell carcinoma with melanocytic differentiation.

Renal cell carcinoma (RCC) is the most common malignant tumor of the adult kidney, and its incidence has been steadily rising. RCC consists of several subtypes, each of which has its own clinical features, and cytogenetic and molecular characteristics. Recognizing histologic patterns of RCC is important not only for correct diagnosis, but also for providing insight into the biological behavior of the tumor and subsequent appropriate medical care for the patient. Pigments other than hemosiderin has been observed in RCC, but none of them have been proved to be melanin. Melanotic tumors, either primary or metastatic, are rare in the kidney. We present an unusual case of melanin-pigmented clear cell RCC with melanocytic differentiation, an unusual variant that may lead to errors in diagnosis and treatment.

Adenocarcinoma, Clear Cell↗
PubMed2001

Renal metastases from thyroid papillary carcinoma: study of sodium iodide symporter expression.

Kidney metastases from thyroid cancer are rare. We report two such patients and demonstrate that the in vivo 131I uptake by the kidney metastasis is associated with high levels of sodium iodide (Na+/I-) symporter (NIS) expression in the first case. Case 1: A 61-year-old woman with papillary thyroid carcinoma-follicular variant (PTC-FV) presented with scapular metastasis. After thyroidectomy and scapulectomy, a 131I posttherapy scan showed left upper quadrant uptake. A 3.0-cm metastatic PTC-FV deposit was removed by partial nephrectomy. Case 2: A 53-year-old woman presented with back pain. A computed tomography (CT) scan showed a 3.5-cm renal mass, a multinodular goiter, and lung metastases thought secondary to a renal cell carcinoma. A unilateral nephrectomy revealed metastatic PTC-FV. After thyroidectomy, a 131I posttherapy scan showed lung and skeletal metastases. NIS immunoreactivity in tumoral tissue was strongly positive in the primary tumor, shoulder, and kidney metastasis in case 1, as well as in the primary tumor in case 2. Spotty, low-level NIS expression was observed in the kidney metastasis in case 2. In conclusion, kidney metastases of PTC-FV may occasionally retain adequate levels of NIS expression, enabling their detection during life. Thus, intense uptake in the abdomen during 131I imaging should not be assumed to be physiological gastrointestinal tract residual radionuclide activity.

Carcinoma, Papillary↗
PubMed2001

Semenogelins are ectopically expressed in small cell lung carcinoma.

Two proteins recovered from cell surface adhesion complexes in a small cell lung carcinoma (SCLC) cell line were identified as fragments of the seminal plasma proteins semenogelin I and semenogelin II. Association of both proteins with the adhesion complexes was induced by epidermal growth factor. Expression of semenogelins was previously thought to be highly specific to seminal vesicles, but Western blot analysis demonstrated that semenogelin II is widely expressed in SCLC cell lines and occasionally in other malignant cell lines. Although semenogelin expression is normally restricted to males, two SCLC cell lines from female patients were also positive for semenogelin II expression. Immunohistochemical analysis demonstrated diffuse expression of semenogelins in 12 of 13 SCLC tumors and focal expression in a minority of lung squamous and adenocarcinomas. Semenogelins were secreted into the medium by cultured SCLC cells, which suggested that these proteins may be useful markers for detecting residual tumor burden or recurrence of SCLC after treatment.

Biomarkers, Tumor↗
PubMed2000

The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting.

NIH sponsored a meeting of medical and veterinary pathologists with mammary gland expertise in Annapolis in March 1999. Rapid development of mouse mammary models has accentuated the need for definitions of the mammary lesions in genetically engineered mice (GEM) and to assess their usefulness as models of human breast disease. The panel of nine pathologists independently reviewed material representing over 90% of the published systems. The GEM tumors were found to have: (1) phenotypes similar to those of non-GEM; (2) signature phenotypes specific to the transgene; and (3) some morphological similarities to the human disease. The current mouse mammary and human breast tumor classifications describe the majority of GEM lesions but unique morphologic lesions are found in many GEM. Since little information is available on the natural history of GEM lesions, a simple morphologic nomenclature is proposed that allows direct comparisons between models. Future progress requires rigorous application of guidelines covering pathologic examination of the mammary gland and the whole animal. Since the phenotype of the lesions is an essential component of their molecular pathology, funding agencies should adopt policies ensuring careful morphological evaluation of any funded research involving animal models. A pathologist should be part of each research team.

Animals↗
PubMed2000

Loss of heterozygosity in P53, BRCA1, and estrogen receptor genes and correlation to expression of p53 protein in ovarian epithelial tumors of different cell types and biological behavior.

Loss of heterozygosity (LOH) of tumor suppressor genes (TSGs) in ovarian epithelial tumors of differing cell types and biological behavior has not been thoroughly investigated. Moreover, there have been conflicting reports correlating LOH of the p53 gene to overexpression of p53 protein. This study evaluated 34 formalin-fixed, paraffin-embedded ovarian epithelial tumors for LOH by polymerase chain reaction (PCR) for the following microsatellite markers: TP53(17p13.1/p53 gene), D17S579(17q/BRCA1 gene), and ESR (6q24-27/estrogen receptor gene). LOH of the TP53 marker was detected in 4 (44%) of 9 informative serous cystadenocarcinomas (SCa) but in 0 of 4 informative clear cell carcinomas (CCa) and 0 of 5 informative serous tumors of low malignant potential (SLMP). LOH of the BRCA1 marker was detected in 5 (83%) of 6 informative SCa, but in 1 (13%) of 8 informative CCa and 1 (14%) of 7 informative SLMP. LOH of the ESR marker was detected in 4 (50%) of 8 informative SCa, but in 0 of 4 informative CCa and 1 (16%) of 6 informative SLMP. p53 protein overexpression was present in 8 of 12 SCa but did not correlate to TP53 LOH. LOH for TP53, D17S579/ BRCA1, and ESR is common in ovarian SCa, and is observed in primary tumors as well as metastases. In contrast, these genetic alterations are less common in CCa and in the biologically less aggressive SLMP tumors. These data suggest different mechanisms of oncogenesis in ovarian epithelial tumors of different cell types and biological behavior.

Adenocarcinoma, Clear Cell↗
PubMed2000

Alveolar soft part sarcoma: the role of prognostic markers.

Alveolar soft part sarcoma (ASPS) is a rare malignant neoplasm characterized by slow growth and indolent behavior. The role of proliferative markers and tumor suppressor genes is unknown in these tumors. To investigate their potential role in diagnosis and prognosis, we studied 13 cases of primary ASPS and 14 metastases and correlated them with clinicopathologic parameters. Immunohistochemistry was performed with anti-p53 and anti-Ki-67 antibodies. Polymerase chain reaction after tumor microdissection was performed to search for possible loss of heterozygosity in chromosomes 1p, 9p, 17q, 22q, and TP53 to identify possible changes that may clarify the histogenesis of these tumors. Four of five (80%) primary ASPS cases were positive for Ki-67 and all of them developed later metastases. One patient whose tumor did not stain for Ki-67 remained free of disease for 9 years. Eleven of 13 (85%) metastases were positive for Ki-67; however, there was no correlation with final outcome. All the primary ASPS cases analyzed for p53 yielded negative results, but two (15%) of 13 metastases were weakly positive. There was no correlation of these markers with prognosis or clinicopathologic parameters. No loss of heterozygosity was found except in one of nine (11%) informative metastases for D1S165 (at 1p36). Our preliminary data suggest that Ki-67-positive immunostaining may be a prognostic indicator for the development of metastases in ASPS.

Adolescent↗
PubMed2000

Squamous cell carcinoma of the thyroid: an aggressive tumor associated with tall cell variant of papillary thyroid carcinoma.

Squamous cell carcinoma of the thyroid (SCT) is an unusual neoplasm thought to arise as a primary tumor or as a component of an undifferentiated carcinoma. The role of p53 and Ki-67 as prognostic indicators in this type of tumor is not known. We studied eight cases of primary SCT. Three cases were analyzed for Ki-67 by immunohistochemistry and for p53 by immunohistochemistry and loss of heterozygosity. Seven patients were women, and one was a man (age range, 31 to 90 years). SCT were firm, were tan with areas of necrosis, and ranged in size from 2 to 8 cm. Histologically, they had islands of squamous cells with spindle cell areas (two of eight). In four of eight cases, SCT was associated with the tall cell variant of papillary carcinoma (TCV). Positive staining for p53 was seen in two of three cases, and in one of three the TCV was also positive for p53. Mean MIB1 labeling index was 30% and 17% in SCT and TCV, respectively. At the time of presentation, six of eight patients had cervical lymph node metastases. In one case, the primary tumor had SCT and TCV; however, only the SCT component metastasized. After mean follow-up of 48 months, one patient had died of disease, five were alive with recurrent or metastatic tumor, and two were lost to follow-up. Primary SCT is an aggressive neoplasm that may be found in association with TCV. p53 expression and high MIB1 labeling index occur in these tumors and may be useful prognosticators.

Adenocarcinoma, Papillary↗
PubMed2000

Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis.

Infiltrating pleomorphic lobular carcinoma (PLC) is an aggressive variant of infiltrating lobular carcinoma. Recently, in situ changes identical to PLC (PLCIS) have been described. The role of prognostic markers and their correlation with therapeutics, clinical outcome, and genetic changes is not well established in PLC. The authors examined 38 cases of this entity to understand better this tumor's biology. Immunohistochemical (IHC) analysis was performed in 21 specimens for estrogen and progesterone steroid receptors, p53, Her 2 (p185), and GCDFP-15. Genomic deoxyribonucleic acid was obtained from microdissected tumor as well as normal control cells, and loss of heterozygosity was investigated at the ESR (16q24), p53 (TP53 17p), Her 2 (17q 11-12), and BRCA 1 (17q12-25) loci. In this series, the average patient age was 57.5 years (age range, 24-92 years). Twenty-seven women were postmenopausal. Tumor size ranged from 1.2 to 25 cm. Six patients were a pathologic stage I; 19, stage II; 12, stage III; and one, stage IV. Histologically, multifocal nodular aggregates of discohesive pleomorphic tumor cells were seen interspersed in dense and fibrotic breast parenchyma. Twenty-nine percent of the specimens demonstrated associated signet ring cells. The remainder had dishesive, globoid, plasmacytoid cells with high-grade nuclear features. PLCIS was identified in 17 of 38 patients (45%), and lobular carcinoma in situ (LCIS) was noted in 8 patients (21%). IHC analysis showed estrogen immunoreactivity in 81%, progesterone in 67%, GCDFP-15 in 71%, and Her 2 in 81% (2+ to 3+ membranous staining) of specimens. Antibodies to p53 stained the tumor cell nuclei in 48% of the tumors. Loss of heterozygosity was identified in 52% of the specimens at the p53 locus, 18% at the ESR locus, 19% to 24% at the Her 2 loci, and 27% to 32% at the BRCA 1 locus. Follow-up was available in 19 patients and ranged from 12 months to 15 years (mean, 73 months). Seven patients had no evidence of disease at last examination (range, 1-15 years), three patients were alive with disease (range, 2-14 years), and nine patients were dead of disease (range, 2 months-9 years). Six patients had subsequent diagnoses of tumor in the contralateral breast. Analysis shows that PLC tends to appear in older postmenopausal women who present with locally advanced disease. PLCIS was found to be associated with PLC 45% of the time. The aggressive clinical course of patients with PLC is supported by tumor immunoreactivity with unfavorable markers Her 2 and p53. Overexpression of Her 2 in PLC may be therapeutically relevant, enabling the use of novel chemotherapeutic drugs like Herceptin. Interestingly, tumors that were Her 2 immunoreactive also maintained estrogen hormone immunoreactivity.

Adult↗
PubMed2000

Pilot trial of the safety, tolerability, and retinoid levels of N-(4-hydroxyphenyl) retinamide in combination with tamoxifen in patients at high risk for developing invasive breast cancer.

PURPOSE: N-(4-hydroxyphenyl) retinamide (¿4-HPR, Fenretinide; R.W. Johnson Pharmaceutical Research Institute, Springhouse, PA) and tamoxifen (TAM) have synergistic antitumor and chemopreventive activity against mammary cancer in preclinical studies. We performed a pilot study of this combination in women at high risk for developing breast cancer. PATIENTS AND METHODS: Thirty-two women were treated with four cycles of 4-HPR, 200 mg orally (PO) for 25 days of each 28-day cycle, and TAM, 20 mg PO once daily for 23 months beginning after 1 month of 4-HPR alone. Tolerability, dark adaptometry, tissue biopsies, and retinoid plasma concentrations (Cp) were evaluated. RESULTS: Symptomatic reversible nyctalopia developed in two patients (6%) on 4-HPR, but 16 (73%) of 22 patients had reversible changes in dark adaptation, which correlated with relative decrease in Cp retinol (P </=.01). Four patients stopped treatment for side effects, and 84% of patients had hot flashes. Other commonly reported (grade </= 2) reversible toxicities included skin and ocular dryness, fatigue, and mood changes. Serum high-density lipoprotein increased and cholesterol decreased from baseline to month 4. Baseline mean +/- SD Cp retinol was 708 +/- 280 ng/mL. Mean +/- SD Cp of 4-HPR, N-(4-methoxyphenyl) retinamide (4-MPR), and retinol after 1 month of 4-HPR were 0.34 +/- 0.21 micromol/L, 0.28 +/- 0.21 micromol/L, and 282 +/- 127 ng/mL, respectively. Mean retinoid Cps did not change after 3 months of 4-HPR + TAM. CONCLUSIONS: TAM administration did not affect Cp 4-HPR or 4-MPR. Reversible nyctalopia correlated with relative decrease in Cp retinol but was not symptomatic for most patients. TAM + 4-HPR has acceptable tolerability for this high-risk cohort.

Administration, Oral↗
PubMed2000

Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and EGFr as prognostic factors in gastric cancer.

Gastric cancer (GC) continues to be a highly aggressive malignancy with poor prognosis and low survival rates. The survival of patients with GC depends mainly on the stage of the disease, with early GC having a 5 year survival of 90-100% and advanced tumors a 5 year survival of 15-25%. The role of other prognostic factors in these tumors is still under investigation. 28 gastric dysplasia, 45 Early GC and 98 Advanced Gastric Cancers were evaluated for expression of the oncogenes p53, c-ErbB2, c-myc and the EGFr in paraffin-embedded material utilizing Avidin-Biotin immunohistochemistry techniques. In 34 cases of GC microvessel density (MVD) was determined in CD34 stained sections. Statistical correlations with stage, histologic type, differentiation degree, location, size, ploidy patterns and overall survival were done. The Mantel-Cox test was performed to evaluate which factors had an independent prognostic value. Both, tumor angiogenesis and p53 protein expression were statistically associated (95% confidence intervals) with overall survival in patients with GC. p53 protein expression was also correlated with cardial location, nodal involvement and tumor stage. c-ErbB2 may recognize a group of highly aggressive well differentiated adenocarcinomas with worse prognosis. c-myc was also significantly enhanced in well differentiated tumors. EGFr showed no significant associations. Mantel-Cox was performed to compare the prognostic value of tumor stage, p53 protein expression and tumor angiogenesis. Tumor angiogenesis was the most important prognostic indicator to predict overall survival in our series. p53 expression was not independent and did not provide additional prognostic information to tumor stage. Our study suggests that angiogenesis as demonstrated by microvessel counts in CD34 stained sections is a significantly important prognostic factor for predicting survival in gastric cancer.

Adult↗
PubMed1999

Sensitization of tumor necrosis factor alpha-resistant human melanoma by tumor-specific in vivo transfer of the gene encoding endothelial monocyte-activating polypeptide II using recombinant vaccinia virus.

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine with potent experimental antitumor activity. Its clinical use in cancer treatment is severely limited by its considerable toxicity after systemic administration, and it is currently confined to isolated limb and organ perfusion settings. In this report, we introduce a novel concept of TNF-alpha-based gene therapy using the TNF-sensitizing properties of endothelial cell monocyte-activating polypeptide II (EMAP-II). We hypothesized that transfer of the EMAP-II gene into established TNF-resistant human melanomas would render these tumors sensitive to subsequent systemic TNF-alpha treatment. To achieve tumor selective gene delivery, we constructed a recombinant vaccinia virus encoding the human EMAP-II gene (vvEMAP). In vitro transfection of human melanoma cells led to the production of EMAP-II by these cells. Supernatants of vvEMAP-transfected tumor cells mediated the induction of tissue factor in endothelial cells. We characterized the pattern of gene expression after systemic administration of a recombinant vaccinia virus encoding a reporter gene in a murine in vivo model of s.c. human melanoma. Gene expression in tumor tissue was increased 100-fold as compared with normal tissue, providing evidence for tumor-selective gene delivery. Finally, human melanomas in nude mice were sensitized in vivo by transferring the EMAP-II gene using vvEMAP. Subsequent systemic administration of TNF-alpha led to tumor regression and growth inhibition of these previously TNF-resistant tumors (P < 0.05). This approach using gene therapy to sensitize primarily unresponsive tumors toward TNF-alpha may enhance the usefulness of TNF-alpha in clinical treatment strategies by increasing the window for the therapeutic application of the cytokine, thus reducing the dose necessary for antitumor responses and subsequently reduce toxicity.

Animals↗
PubMed1999

The Tall cell variant of papillary carcinoma of the thyroid: cytologic features and loss of heterozygosity of metastatic and/or recurrent neoplasms and primary neoplasms.

BACKGROUND: The Tall cell variant of papillary carcinoma of the thyroid (TCV) is characterized by the proliferation of oxyphilic, tall, columnar cells with a height-to-width ratio of at least 2:1. TCV exhibits more aggressive clinical behavior than conventional thyroid papillary carcinoma (CPC). Cytologic features suggestive of TCV have been described in fine-needle aspiration material from primary tumors. Similarly, loss of heterozygosity (LOH) for chromosome 1 (D1S243) and the p53 gene (TP53) have been reported in TCV but not in CPC, thus making exploitation of this genetic feature a potential tool for molecular discrimination between these two neoplasms. METHODS: Cytology samples of metastatic and/or recurrent neoplasms (M/R) (12 cases) and 7 cases of primary TCV obtained from 12 patients were evaluated. The cytologic findings of these cases were compared with previously published findings. Microdissection and polymerase chain reaction for LOH for chromosome 1 and p53 (D1S243 and TP53 markers) were performed on cytologic smears from 6 cases of M/R tumors and 3 cases of primary tumors. RESULTS: More then 50% of M/R showed atypical follicular cells with enlarged nuclei, granular chromatin, nuclear grooves, pseudoinclusions, and abundant finely granular cytoplasm. Cells were disposed in monolayers (58%) and papillary clusters (50%). Similar findings were present in cases of primary TCV. LOH studies showed that 4 of 6 M/R were noninformative and 2 of 3 cases of primary TCV were informative for the D1S243 marker; however, in contrast with previously published reports, no LOH was detected for the markers evaluated. CONCLUSIONS: M/R and primary TCV have similar cytologic features. Additional studies of larger series of M/R and primary TCV should be performed to delineate further any potential application of LOH for chromosome 1 and the p53 gene as a tool for diagnosing TCV with cytologic preparations. Cancer (Cancer Cytopathol)

Adult↗
PubMed1999

Utilization of microdissection and the polymerase chain reaction for the diagnosis of adrenal cortical carcinoma in fine-needle aspiration cytology.

BACKGROUND: Loss of heterozygosity (LOH) for several tumor suppressor genes (including loci on 3p, 1p, and 17p,) has been documented in surgical specimens of adrenal cortical carcinomas (ACCA) without accompanying losses in benign hyperplastic and adenomatous adrenal cortical lesions (ACL). This disparate pattern of LOH raises the possibility of exploitation of these differences for diagnostic utilization. Cytologic differentiation of benign versus malignant ACL may be impossible based solely on fine-needle aspiration (FNA) material. The authors attempted to extrapolate the genetic findings on surgical specimens to FNA specimens of ACL to determine whether LOH studies could be utilized as a definitive diagnostic tool. METHODS: Microdissection of archival material was performed on FNAs of ten ACCAs (stained with the Papanicolaou and Diff-Quik stains) with corresponding histologic material (stained with hematoxylin and eosin), one FNA of a benign ACL, and three touch preparations of benign adrenal cortex. LOH analysis was performed by polymerase chain reaction (PCR) with flanking markers for the following putative tumor suppressor genes: p53 (17p13; TP53), 1p (1p36; D1S165), and the von Hippel-Lindau gene at 3p25 (D3S1038 and D3S1110). RESULTS: Similar results were obtained with cytologic and histologic material. As expected, benign ACL showed no LOH for the markers examined. Of the informative ACCA cases, 70% showed LOH for at least 1 of the 3 markers tested on both FNA and histologic samples. For all cases with amplifiable DNA, there was a 100% concordance rate for LOH between cytologic and histologic material, with at least 7 of the 10 cytologic samples originating from metastatic lesions and all of the surgical material originating from the primary adrenal neoplasm. CONCLUSIONS: The results of this study suggest that the combination of microdissection and PCR for LOH of p53, 1p, and 3p25 from FNA material has the potential to be utilized to distinguish ACCA from benign ACL in informative cases. It also shows a 100% concordance rate between metastatic and primary ACCAs for the losses observed, a finding that can be extremely useful for the definitive identification of metastatic lesions. Archival cytologic preparations of ACCA are a reliable source of DNA for LOH studies. [See editorial counterpoint on pages 173-5 and reply to counterpoint on pages 176-7, this issue.] Cancer (Cancer Cytopathol)

Adrenal Cortex Neoplasms↗