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PubMed2001

Laser capture microdissection and proteomics: possibilities and limitation.

Tissue heterogeneity has always limited the information available from analysis of biological samples in the study of disease. Several approaches have been developed to address this problem, with laser capture microdissection (LCM) emerging as one of the methods of choice. LCM has been extensively used in combination with mutation detection studies and analyses of gene expression at the mRNA level and its potential in proteomics-based research is beginning to be realised. Here we review the progress made to date in the analysis of proteins in LCM-captured material and evaluate the scope and limitations of this approach.

Antibodies↗
PubMed1988

Vitamin E distribution in ocular tissues following long-term dietary depletion and supplementation as determined by microdissection and gas chromatography-mass spectrometry.

Vitamin E is thought to be important for protection of polyunsaturated fatty acids (PUFA) from oxidative damage. A microbiochemical procedure using microdissection and gas chromatography-mass spectrometry was developed to determine vitamin E distribution in ocular tissues in a rodent model, with the eventual goal of using it in a study of phototoxic degeneration of the retina, where PUFA oxidation is potentially the causal mechanism. Sample preparation was achieved by freeze-drying the retina followed by micro-dissection to obtain the desired structures for analysis. A deuterated alpha-tocopherol internal standard is added to the tissue sample before extraction and derivatization which are achieved in a single step. The data presented show the vitamin-E content in various structures of the retina, particularly the outer segments and retinal pigment epithelium (RPE); however, the vitamin E content of other ocular tissues is also included. Data were obtained from albino and pigmented rats receiving vitamin E-depleted, supplemented, and regular chow diets, and from rabbits and cats receiving regular chow diets formulated for each species. Within all dietary groups the highest concentration of vitamin E was located in the RPE followed by the outer segments of the photoreceptor cells. Other ocular tissues consistently contained lower amounts of vitamin E. Different tissues were depleted of vitamin E at different rates and this points out the importance of determining vitamin E levels in tissues of interest in studies on the consequences of dietary depletion.

Animals↗
PubMed2004

Malignant transformation of endometriosis: application of laser microdissection for analysis of genetic alterations according to pathological changes.

Endometriosis is considered to be a possible precancerous disease. Pathologically, we observed malignant transformation of endometriosis to clear cell carcinoma or endometriotic carcinoma of the ovary, via the step of atypical endometriosis. Pathological changes reflected genetic alterations. In cases of clear cell carcinoma, we assessed K- ras mutations in regions of normal endometriosis, atypical endometriosis, and clear cell carcinoma, and obtained tissue samples by laser microdissection. We found that K- ras mutations were associated with malignant transformation of clear cell carcinoma. The present results indicate that laser microdissection can be used to combine assessment of genetic and pathological changes.

Adenocarcinoma, Clear Cell↗
PubMed2005

Keratinocyte growth factor-1 expression in healthy and diseased human periodontal tissues.

OBJECTIVES: Keratinocyte growth factor-1 (KGF-1) is up-regulated in chronic inflammation and specifically stimulates epithelial cell proliferation by signaling through the epithelial-specific keratinocyte growth factor receptor (KGFR). We examined KGF-1 and KGFR protein and gene expression in healthy and diseased periodontal tissues. METHODS: Tissues were collected from patients with periodontal health or disease, immediately frozen and stained for KGF-1 and KGFR protein expression. Laser capture microdissection of epithelial and connective tissue cells with reverse transcription-polymerase chain reaction (RT-PCR) examined KGF-1 and KGFR gene expression profiles and enzymatic digestion with heparitinase, chondroitinase ABC or pre-treatment with suramin examined epithelial surface molecule interactions with KGF-1. RESULTS: In tissues collected from healthy patients, KGF-1 protein localized to areas of junctional and basal oral epithelial cells and was significantly increased in periodontal pocket epithelium (p<0.01) and in the oral epithelium (p<0.05) of disease-associated tissues. KGFR localized to the junctional and the parabasal cells of oral epithelium, with the relative staining intensity being increased in disease-associated pocket epithelium (p<0.05). Laser capture microdissection with RT-PCR confirmed KGF-1 and KGFR were specifically expressed by connective tissue and epithelium, respectively. KGF-1 localization to epithelial cells was largely eliminated by suramin pre-treatment, indicating interaction with the KGFR. CONCLUSIONS: KGF-1 and KGFR proteins are expressed in healthy periodontal tissues but significantly increased in diseased periodontal tissues. We hypothesize up-regulation of KGF-1 and KGFR protein associated with disease regulates epithelial cell behavior associated with onset and progression of periodontal pocket formation.

Fibroblast Growth Factor 7↗
PubMed2006

Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection.

Much work has been done to develop tumor-targeting antibodies by selecting a phage antibody library on cancer cell lines. However, when tumor cells are removed from their natural environment, they may undergo genetic and epigenetic changes yielding different surface antigens than those seen in actual cases of cancer. We developed a strategy that allows selection of phage antibodies against tumor cells in situ on both fresh frozen and paraffin-embedded tissues using laser capture microdissection. By restricting antibody selection to binders of internalizing epitopes, we generated a panel of phage antibodies that target clinically represented prostate cancer antigens. We identified ALCAM/MEMD/CD166, a newly discovered prostate cancer marker, as the target for one of the selected antibodies, demonstrating the effectiveness of our approach. We further conjugated two single chain Fv fragments to liposomes and demonstrated that these nanotargeting devices were efficiently delivered to the interior of prostate cancer cells. The ability to deliver payload intracellularly and to recognize tumor cells in situ makes these antibodies attractive candidates for the development of targeted cancer therapeutics.

Antibodies, Neoplasm↗
PubMed2003

Tensor fasciae latae perforator flap.

The tensor fasciae latae perforator flap and a new technique, named microdissection, for one-stage accurate formation of a thin flap were presented. Microdissection enables the perforator in the adipose tissue to be used as a lengthened pedicle, and the flap can be transferred without adding and reducing excess fat tissue to the recipient and donor sites. This microdissected thin tensor fasciae latae perforator flap can be used conveniently in many aspects of reconstructive surgery, especially in cases of severe bum scar contracture of the extremities.

Adult↗
PubMed2002

Tie-2 and angiopoietin-1 expression in human thyroid tumors.

Tie-2 is an endothelial cell-specific receptor tyrosine kinase involved in vascular maturation and remodeling. Although its expression is considered to be restricted to vascular endothelial cells and hematopoietic progenitors, our immunohistochemical and in situ hybridization studies showed that Tie-2 and its ligand, angiopoietin (Ang)-l were expressed not only in benign and malignant human thyroid tumor cells but also in hyperplastic regions of adenomatous goiter. To confirm the expression in these tissues further, we used a laser capture microdissection system to isolate epithelial tumor cells from tissue specimens selectively, and demonstrated the expression of Tie-2 and Ang-1 mRNAs in tumor cells by RT-PCR analysis. Furthermore, Tie-2 and Ang-1 mRNAs and proteins were also detected in rat thyroid cell lines, FRTL-5 and PCCL-3. Our results suggest that Ang-1/Tie-2 signaling may be involved in the proliferation of thyroid epithelial cells.

Adenocarcinoma, Follicular↗
PubMed2003

[Detailed mapping and clinical significance of loss of heterozygosity on 9p13-23 in laryngeal squamous cell carcinoma by microsatellite analysis].

BACKGROUND & OBJECTIVE: Microsatellites are the repeated DNA sequences scattered widely within the biological genomes and closely linked with many important genes. In carcinogenesis, microsatellites often display loss of heterozygosity(LOH) as tumor suppressor genes. Some microsatellite loci often exist in the hot spots of LOH at high frequency in some specific maligances. The tumor suppressor genes, which are associated with the development and progression of the tumor, possibly harbor in the vicinity of these hot spots. Therefore, the study of LOH by microsatellite analysis is an important way to detect the putative tumor suppressor genes. This study was designed to refine the hot spots of LOH on 9p13-23 in laryngeal squamous cell carcinoma and compare the correlation between the incidence of microsatellite LOH and the clinicopathological parameters. METHODS: Tumor tissues were obtained from paraffin embedded sections with microdissection. Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform. Polymerase chain reaction(PCR) amplification and denaturing gel electrophoresis were performed on a set of 42 laryngeal squamous cell carcinoma and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23. The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological characteristics in the patients with squamous cell carcinoma of larynx. RESULTS: (1)Of the 42 laryngeal cancers, 41(97.6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23. The most frequently deleted marker was D9S162 in 17 of the 19 (89.5%) informative samples. The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80.0%). LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50.0%). (2)Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23. (3) Multiple LOH (>or= 4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic squamous cell carcinoma or cervical lymph node metastasis than those over 60 years, with glottic squamous cell carcinoma or without cervical lymph node metastasis (P< 0.01,P< 0.01,P< 0.05, respectively). On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 squamous cell carcinoma of larynx. CONCLUSION: These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal squamous cell carcinoma. Multiple genetic alterations are probably implicated in supraglottic squamous cell carcinoma with cervical lymph node metastasis in younger patients.

Adult↗
PubMed2004

Detailed deletion mapping of loss of heterozygosity on 9p13-23 in laryngeal squamous cell carcinoma by microsatellite analysis.

BACKGROUND: This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters. METHODS: Tumor tissues were obtained from paraffin embedded sections with microdissection. Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform. Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23. The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx. RESULTS: Of the 42 laryngeal cancers, 41 (97.6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23. The most frequently deleted marker was D9S162 in 17 of the 19 (89.5%) informative samples. The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80.0%). LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50.0%). Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23. Multiple LOH (> or = 4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis (P < 0.01 or 0.01, 0.05, respectively). On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx. CONCLUSIONS: These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal SCC. Multiple genetic alterations are probably implicated in supraglottic SCC with cervical lymph node metastasis in younger patients.

Adult↗
PubMed1983

[Sampling of tissue from microscopic areas of the spinal cord of the chick embryo. Description of the technic and application to the study of enzymes metabolizing acetylcholine].

In the present communication we describe a very simple procedure which allows measuring the specific activity of cholinergic enzymes (Acetylcholinesterase and cholinacetyltransferase) in microscopical areas of chick embryo spinal cord. Microhomogenates were prepared as follows: i) a number of fresh cryostat sections (20 mu thick) were stained with toluidine blue; ii) the adjacent unstained sections were microdissected under stereomicroscope and tissue fragments were collected from different areas (lateral, medial and posterior columns; anterior, lateral and posterior bundles). Tissue fragments were dissolved in 10 mM sodium-phosphate buffer pH 7.4 (20-40 sections). Protein assay was performed according to Bradford (1976). AChE and ChAc were measured by radiochemical methods of Fonnum (1969, 1970). In lumbar segments of 18-day chick embryo spinal cord AChE was found in all structure investigated, by contrast ChAc was localized almost exclusively in lateral somatomotor comumns. This result indicates that ChAc can be considered a specific marker for motoneurons. The ontogeny of the cholinergic enzymes in various areas of the chick embryo spinal cord has been investigated.

Acetylcholine↗
PubMed2005

Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?

Using quantitative reverse transcription-polymerase chain reaction (RT-PCR), reference genes are utilized as endogenous controls for relative quantification of target genes in gene profiling studies. The suitability of housekeeping genes for that purpose in prostate cancer tissue has not been sufficiently investigated so far. The objective of this study was to select from a panel of 16 potential candidate reference genes the most stable genes for gene normalization. Expression of mRNA encoding ACTB, ALAS1, ALB, B2M, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, POLR2A, PPIA, RPL13A, SDHA, TBP, UBC, and YWHAZ was examined in matched, microdissected malignant and nonmalignant tissue specimens obtained from 17 nontreated prostate carcinomas after radical prostatectomy by real-time RT-PCR. The genes studied displayed a wide expression range with cycle threshold values between 16 and 37. The expression was not different between samples from pT2 and pT3 tumors or between samples with Gleason scores <7 and >or=7 (P>0.05). ACTB, RPL13A, and HMBS showed significant differences (P<0.02 at least) in expressions between malignant and nonmalignant pairs. All other genes did not differ between the matched pairs, and the software programs geNorm and NormFinder were used to ascertain the most suitable reference genes from these candidates. HPRT1, ALAS1, and K-ALPHA-1 were calculated by both programs to be the most stable genes covering a broad range of expression. The expression of the target gene RECK normalized with HRPT1 alone and with the normalization factors generated by the combination of these three reference genes as well as with the unstable genes ACTB or RPL13A is given. That example shows the significance of using suitable reference genes to avoid erroneous normalizations in gene profiling studies for prostate cancer. The use of HPRT1 alone as a reference gene shown in our study was sufficient, but the normalization factors generated from two (HRPT1, ALAS1) or all three genes (HRPT1, ALAS1, K-ALPHA-1) should be considered for an improved reliability of normalization in gene profiling studies of prostate cancer.

Aged↗
PubMed2004

Prostate cancer invasion is influenced more by expression of a CD44 isoform including variant 9 than by Muc18.

The standard form of cell adhesion glycoprotein CD44 is a metastasis suppressor in prostate cancer. However, we previously showed by RT-PCR and Western blotting that cancer overexpresses unique CD44 variant v7-v10 isoforms. Muc18 is another cell adhesion marker reportedly overexpressed by prostate cancer. Matched frozen section-confirmed tumor and benign tissues were harvested from 10 prostatectomy specimens and tumor was microdissected from two lymph node metastases. Tissues were homogenized for RNA preparations, and RT-PCR was performed for the CD44v7-v10 sequence. In cultured prostate cancer cells, we caused RNA interference against CD44v9 and/or Muc18. We used PC3M cells and a derivative cell line called G(s)alpha, that constitutively expresses this G-protein and is more invasive. Lipofection was performed for a green fluorescent protein plasmid and for two 22-mer DNA fragments, cloned into a plasmid expression vector to generate hairpin, interfering dsRNA. Assays for invasion into Matrigel, a basement membrane matrix, were performed in 4-5 experiments. RT-PCR demonstrated expression of a 608 bp band representing CD44v7-v10 or a 638 bp band of CD44v6-v10 in prostate cancer tissues and metastases but not benign tissue. Cultured G(s)alpha cells overexpressed CD44v9 by comparison with PC3M cells. At 90 h after 6-hour lipofection, protein silencing was evident by Western blots. Silencing the CD44v9 expression reduced invasiveness into Matrigel to 21.6+/-7.0% in PC3M cells (P<0.001) and 31.2+/-18.3% in G(s)alpha cells (P=0.001), compared to cells exposed to transfection vehicle alone. Silencing Muc18 expression reduced invasiveness to 76.9+/-13.5% of the control value in PC3M cells (P<0.05) and 84.8+/-29.9% in G(s)alpha cells (P=0.18). Prostate cancer invasion is facilitated more by its overexpression of CD44 variant 9 than by Muc18. Its relative overexpression by G(s)alpha cells is a novel finding, suggesting a link between signal transduction and cell adhesion marker expression.

Antigens, CD↗
PubMed1999

Definition of ocular antigens in ciliary body and retinal ganglion cells by the marker antibody pANCA.

PURPOSE: A subset of patients with anterior uveitis express the marker, perinuclear anti-neutrophil cytoplasmic antibody (pANCA). In this study, recombinantly isolated pANCA monoclonal antibodies were used to search for ocular cells expressing the pANCA antigen. METHODS: Paraffin sections of human ocular tissues obtained after death were analyzed by immunohistochemistry to identify cell types expressing pANCA antigen. Microdissected eye-bank ocular tissue was characterized by western blot analysis to confirm antigen expression and identify candidate protein species. RESULTS: Immunohistochemical analysis with pANCA monoclonal antibodies revealed cytoplasmic antigen expression in retinal ganglion cells and ciliary body epithelium. pANCA antigen expression was restricted to tissues bearing these cell types by western blot analysis. A common set of epitope-positive protein species was shared by the two tissues (28 kDa, 80 kDa, and 90 kDa). Comparison of ocular tissues from seven subjects revealed no heterogeneity in antigen expression. CONCLUSIONS: In this study, novel cytoplasmic antigens of the pANCA marker antibody expressed in ciliary body and retinal tissue were identified. Validation of these antigens as targets of inflammation in pANCA+ uveitis requires further biochemical and immunologic analysis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Using fluorescence-based human androgen receptor gene assay to analyze the clonality of microdissected dendritic cell tumors.

The clonality of dendritic cell proliferations arising in patients with previously diagnosed B-cell non-Hodgkin lymphoma has not been determined. The highly polymorphic human androgen receptor gene (HUMARA) can be used to assess the pattern of X-chromosome inactivation and, hence, the clonality of tumors in female patients. In this study, specimens from 2 female patients with dendritic cell tumor following low-grade B-cell non-Hodgkin lymphoma were analyzed. Microdissection was performed on tissue sections to obtain representative tissues for analysis. The HUMARA polymerase chain reaction was modified to include a fluorochrome (6-carboxyfluorescein)-labeled primer so the product could be assessed with the ABI Genescan Analysis program for the Macintosh (Applied Biosystems, Foster City, Calif). Our results indicate that dendritic cell proliferations associated with low-grade B-cell non-Hodgkin lymphoma are clonal lesions. Previous microdissection is very helpful in obtaining the desired cell populations for study. The use of a fluorescent primer coupled with the Genescan System is a novel, highly sensitive, quantitative system that avoids the use of radioactive materials.

Cell Division↗
PubMed1995

Microdissection and molecular genetic analysis of HER2/neu in breast carcinoma.

Precise correlation of histomorphology with molecular genetic analysis is difficult in tissues composed of heterogeneous cell populations. We describe here a novel microdissection technique employed to correlate HER2/neu (HER2) immunohistochemical staining with HER2 genetic analysis in formalin-fixed, paraffin-embedded breast tissue. Fourteen invasive ductal carcinomas were selected from the pathology files of Memorial Sloan-Kettering Cancer Center that had been immunostained for HER2. Seven tumors showed typical membrane immunoreactivity and seven were negative. A dissecting microscope was then used to isolate minute (< or = 1 mm x 1 mm) areas of invasive carcinoma and normal breast tissue for molecular study. To document the type of cell sample submitted for polymerase chain reaction (PCR) analysis, each microdissected piece of tissue was photographed prior to removal from the glass slide. A preliminary study of four cases compared the results of PCR and genetic analysis using microdissected hematoxylin and eosin (H & E)-stained tissue, unstained dewaxed tissue, and destained dewaxed tissue in four specimens. Similar results were obtained with all three tissue preparations. Thereafter, H & E stained sections were selected as the tissue preparation of choice because tissue details were seen more clearly. There was complete correlation of immunohistochemical staining and HER2 analysis by PCR in all 14 cases. In the final 10 cases, the PCR product was resolved by gel electrophoresis and quantified by optical densitometry. Fourfold to eightfold amplification of HER2 was found in the five tumor specimens that immunohistochemically stained for HER2. A single copy of HER2 was found in all HER2-negative tumors and in normal breast tissue. We conclude that it is possible to quantify gene amplification of HER2 in minute samples of H & E-stained normal and malignant breast tissue. This microdissection technique can be applied to correlative histologic--molecular genetic analysis in a wide variety of tumor types.

Breast Neoplasms↗
PubMed2004

Direct and repeat uses of tissue sections as templates for liquid-phase polymerase chain reaction amplification: applications and implications.

The liquid-phase polymerase chain reaction (PCR) technique is the most commonly used method for the amplification of genetic materials, although it requires the lysis of cells for DNA or RNA extraction, making it impossible to visualize the distribution and subcellular localization of the biomolecules. This study intended to assess whether tissue sections may be directly and repeatedly used as templates for liquid-phase PCR amplifications. Consecutive paraffin sections of breast tissues were placed on gamma-methacryloxypropyltrimethoxysilane-coated microscopic cover glasses perforated with a diamond knife into strips. After hematoxylin and eosin or immuno-staining, the strip of interest was inserted into a PCR tube for amplifications, and the adjacent strip with the same tissue was subject to microdissection, DNA extraction, and PCR amplifications. To use the strip repeatedly, it was transferred into a new PCR tube and amplified with a new primer set, after an initial amplification for 5 to 7 cycles. Then, initially amplified samples were amplified to a total of 40 cycles. An equal volume of PCR products from the strip and DNA extract were loaded side by side for electrophoresis and detection. The strip and DNA extract from the same tissue yielded a very comparable quality and quantity of PCR products with the same primer sets. The strip, however, could be repeatedly used for PCR amplifications with substantially more primer sets. In addition, the strip could be used for immunohistochemical or other molecular assays after PCR amplifications. Further studies with the same protocol on strips containing chromosomal spreads generated similar results.

DNA↗
PubMed2000

Expression profile of an androgen regulated prostate specific homeobox gene NKX3.1 in primary prostate cancer.

PURPOSE: NKX3.1, a member of the family of homeobox genes, exhibits prostate tissue specific expression and appears to play a role in mouse prostate development. Rapid induction of NKX3.1 gene expression in response to androgens has also been described. On the basis of the established role of androgens in prostatic growth and differentiation and studies showing an association of aberrant homeobox gene expression with the neoplastic process, we hypothesize that alterations of NKX3.1 gene expression play a role in prostate tumorigenesis. MATERIALS AND METHODS: NKX3.1 expression was analyzed in matched, microdissected normal and tumor tissues from 52 primary prostate cancer specimens from radical prostatectomy by semiquantitative RT-PCR and in situ hybridization and correlated with the clinicopathologic features. NKX3.1 expression was quantified as differential expression between matched tumor and normal tissues and was grouped as overexpression in tumor tissue, reduced expression in tumor tissue and no change between tumor and normal tissues. Androgen regulation of NKX3.1 expression was also studied in LNCaP cells. Androgen receptor (AR) expression in prostate tumor and normal tissue was correlated with NKX3.1 expression. RESULTS: Comparison of NKX3.1 expression between normal and tumor tissues revealed overexpression in 31% tumor specimens (16 of 52), decreased expression in 21% tumor specimens (11 of 52) and no change in 48% specimens (25 of 52). When these expression patterns were stratified by organ confined and non-organ-confined tumor, a higher percentage of patients exhibited NKX3.1 overexpression in non-organ confined tumor (40%) versus organ confined tumor (22%). Elevated NKX3.1 expression significantly correlated with tumor volume and serum prostate specific antigen (PSA) level in the NKX3.1 overexpression group (p<0.05). Metastatic prostate cancer cell lines did not exhibit mutations in the protein coding sequence of NKX3.1. Additionally, the NKX3.1 expression correlated with AR expression (p<0.01) in vivo in human prostate tissues. Comparison of PSA and NKX3.1 expression in response to androgen revealed a rapid androgen mediated induction of NKX3.1 expression in LNCaP cells. In situ hybridization analysis of representative specimens confirmed RT-PCR observations. CONCLUSIONS: These results suggest an association of NKX3.1 with a more aggressive phenotype of carcinoma of the prostate. Correlation of AR expression with NKX3.1 in human prostate tissues underscores the androgen regulation of NKX3.1 in the physiologic context of human prostate tissues.

Androgens↗
PubMed1989

Surgical treatment of medullary thyroid carcinoma in a thirteen-year-old girl with MEN 2B.

Patients with palpable medullary thyroid carcinoma (MTC) have lymph node metastases in 90% of cases. In most series such patients continue to have elevated serum calcitonin (CT) levels after surgery indicating residual tumor tissue. We attempted a microdissection technique for the treatment of MTC. "Micro" refers not to a small incision or a limited exploration but to a more safe operation associated with good lighting and magnification and minimal bleeding. This technique was used in a 13-year-old girl with multiple endocrine neoplasia type 2B (MEN 2B). The prognosis for MTC in MEN 2B is worse than for sporadic MTC and the MTC of MEN 2A. Every possible effort should be made to remove all tumor tissue in MEN 2B patients with MTC. In this case the pathologist found bilateral MTC and metastases in eight of 129 lymph nodes removed. The preoperative stimulated CT levels, which were markedly elevated, decreased to near normal postoperatively.

Adolescent↗