ADASP recommendations for processing and reporting of lymph node specimens submitted for evaluation of metastatic diseaseLawrence, W.; Pathology, Association
doi: 10.1007/s004280100412pmid: 11764377
It is well known that different pathologists in different laboratories follow different protocols for the processing and examination of these specimens. There is also extensive literature (some of which is summarized in the references appended to the present report) on the likelihood of identifying metastases of varying sizes with different methods of preparation, as well as on the clinical significance of this identification, which varies not only from site to site but also from report to report on the same site. The Association of Directors of Anatomic and Surgical Pathology (ADASP) has reviewed this literature as well as the personal experience of its own members to present a set of recommendations for lymph node biopsies, lymph node dissections, sentinel node biopsies, lymph node fine needle aspiration (FNA) and core needle biopsies. It should be noted that these recommendations are intended specifically for lymph nodes being studied for metastatic neoplasms, and are not intended to apply to lymph nodes being evaluated for lymphoma, infections, and other disease processes. They are, however, formulated generically enough to apply regardless of whether the primary tumor is a carcinoma of the breast, carcinoma of the prostate, melanoma, or any other malignant, potentially metastasizing tumor. The Association has published numerous documents with recommendations for reporting surgical pathology specimens involving particular organ sites (for example, breast, pancreas, thyroid, etc.) However, the Association has not yet considered the generic question of dealing with lymph node specimens in which the intent is to search for and document the presence of metastatic disease. We are also unaware of guidelines for pathologists published by any other organization on this subject.
Expression of MUC5AC apomucin in transitional cell carcinomas of the urinary bladder and its possible role in the development of mucus-secreting adenocarcinomasKunze, Ekkehard; Francksen, Bernd; Schulz, Harald
doi: 10.1007/s004280100429pmid: 11764379
The histogenesis of primary nonurachal mucus-producing adenocarcinomas of the urinary bladder including signet ring cell carcinomas remains to be elucidated, since the normal bladder contains neither columnar nor mucus-secreting glandular epithelium. Based upon the assumption that adenocarcinomas may develop secondarily from pre-existent transitional cell carcinomas (TCC) by a metaplastic process, it was the purpose of the current immunohistochemical study to analyze whether urothelial carcinomas are capable of secreting MUC5AC apomucin, using the monoclonal antibody 45M1. This antibody has been initially demonstrated to strongly react with the mucus-producing columnar cells of the surface gastric epithelium, recognizing a specific epitope located on the peptide core of glycoproteins as major components of mucins. Nine of 64 uniformly differentiated papillary (14.1%) and 5 of 66 nonpapillary (solid) TCC with a uniform urothelial differentiation (7.6%) expressed the MUC5AC antigen, yielding an overall incidence of 10.8%. Transitional cell carcinomas with a focally altered cellular and structural differentiation (squamous cell, pseudoglandular, true glandular and mixed differentiation) stained positively in a substantially higher percentage of 43.8% (21 of 48 cases). A positive immunoreactivity was also observed in 3 of 19 mixed transitional cell and nonurothelial carcinomas. The tumor-associated resurgence of normally cryptic MUC5AC antigenic determinants in transitional cell carcinomas is considered as a re-expression of oncofetal antigenicity, probably as a result of the embryologic origin of the urinary bladder from the pluripotent tissues of the cloacal endoderm and the mesodermal wolffian ducts. Our findings may help to better understand the histogenetic development of mucus-secreting vesical adenocarcinomas from pre-existent urothelial carcinomas.
Reduced human mismatch repair protein expression in the development of precancerous skin lesions to squamous cell carcinomaLiang, Sheng-Ben; Furihata, Mutsuo; Takeuchi, Tamotsu; Sonobe, Hiroshi; Ohtsuki, Yuji
doi: 10.1007/s004280100445pmid: 11764381
Loss of human mismatch repair (hMSH2) gene function has been linked to hereditary non-polyposis colorectal cancer (HNPCC), Muir-Torre syndrome (MTS), and sporadic cancers, excluding skin cancers unrelated to MTS. We immunohistochemically examined 125 squamous cell carcinomas (SCCs) using a monoclonal antibody to the hMSH2 protein and compared the results with those for 106 precursor lesions of SCC, consisting of actinic keratosis (AK), Bowenoid type of actinic keratosis (BAK), and Bowen's disease (BOD). In contrast to the homogeneous immunoreactivity of proliferating cells composed of AK, BAK, and BOD, heterogeneous and diminished immunostaining to hMSH2 was observed in tumor cells of SCCs examined. In addition, two SCCs (2 of 125; 1.6%) at multiple loci exhibited a complete lack of immunoreaction to hMSH2. Immunohistochemical staining of hMSH2 was semiquantitatively scored as 0 (0% of total cells examined), 1 (less than 10%), 2 (10-50%), or 3 (more than 50%). Percentage preservation of and average score for hMSH2 expression in normal, AK, BAK, BOD, and SCC were 56% and 2.06, 100% and 2.80, 94% and 2.88, 83% and 2.78, 63% and 2.36, respectively. The percentage preservation of and average scores for hMSH2 in AK, BAK, and BOD were significantly higher than those in presumably normal skin (P<0.01). There were no significant differences in the percentage preservation of and average scores for hMSH2 between presumably normal skin and SCC. The score for hMSH2 expression was significantly correlated with score for sun exposure in presumably normal skin of each lesion (R=0.70). These findings for hMSH2 expression in precursor lesions and SCC suggest that promotion or activation of hMSH2 expression may be induced by the increased DNA damage caused by sun exposure and that diminished expression of it might occur according to the transformation from precancerous lesions to SCC.
Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanomaDöme, Balázs; Somlai, Beáta; Ladányi, Andrea; Fazekas, Károly; Zöller, Margot; Tímár, József
doi: 10.1007/s004280100451pmid: 11764382
We analyzed the immunohistochemical expression of the metastasis-associated protein, CD44v3, in 46 primary human malignant melanomas (MMs). This is the first time that the v3 splice variant of CD44 was found to be expressed in human melanomas (15 of 46), ranging from 3% to 35% of the cell population in the positive tumors. The expression of CD44v3 was observed in tumors thicker than 1.0 mm, and one-third of these tumors proved to be positive irrespective of the thickness. Patients were followed for a minimum of 61 months. The onset of lymph node or organ metastases occurred not later than 58 months and 60 months, respectively. Of the 15 CD44v3 positive tumors, 14 were observed in the organ metastatic tumor group, comprising the majority of those cases (14 of 21), and this association proved to be statistically significant compared with the non-metastatic (P<0.05) and lymph-node metastatic cases (P<0.01). CD44v3 expression in melanoma was also confirmed at the protein and messenger (mRNA) level in several human melanoma cell lines using flow cytometry and reverse transcriptase polymerase chain reaction analysis. In parallel to CD44v3, MMP-2 expression (determined using immunohistochemistry) was significantly elevated (P<0.05) but only in the organ metastatic group of MM. The 5-year survival of patients having thicker tumors than 1.0 mm (where v3 expression occurred) who had CD44v3+ tumors was significantly lower than those of the negative ones (35.7% versus 68.2%, respectively; P=0.025). Finally, we observed that the CD44v3-expressing tumors were characterized by significantly higher MMP-2 expression than the CD44v3-negative tumors (P<0.001), indicating a possible correlation between CD44v3- and MMP-2-positive phenotype and the organ metastatic potential of MM.
Vascular endothelial growth factor expression, angiogenesis, and necrosis in renal cell carcinomasHemmerlein, Bernhard; Kugler, Alexander; Özisik, Rehyan; Ringert, Rolf-Hermann; Radzun, Heinz-Joachim; Thelen, Paul
doi: 10.1007/s004280100464pmid: 11764385
Rapidly growing tumors often develop necrosis. In the present study the expression of vascular endothelial growth factor (VEGF) was investigated and compared to microvessel density and necrosis of renal cell carcinomas. In the tumor-host interface the microvessel density was significantly increased compared to central tumor areas. Tumor necrosis was associated with a decrease of microvessel density and an increase of the VEGF protein expression within the perinecrotic rim. VEGF protein was focally upregulated in vital tumor tissue. An increase of the apoptotic rate of endothelia and vital tumor tissue in tumors with necrosis could not be detected. VEGF(121,165) mRNA was decreased in proliferatively active carcinomas compared to less proliferative tumors. Multicellular renal cell cancer spheroids as a model of chronic hypoxia developed central apoptosis but no necrosis. VEGF was upregulated in the spheroid. Tumor microvessels expressed matrix metalloproteinase -2 and -9 and an incomplete pericyte covering in comparison to tumor-free tissue indicating immature active angiogenesis. We conclude that highly proliferative renal cell carcinomas outgrow their vascular supply and develop chronic hypoxia inducing a decrease of proliferation and an increase of VEGF expression. However, chronic hypoxia does not cause significant necrosis or apoptosis. Tumor necrosis is more likely induced by acute hypoxia due to immature microvessels. Furthermore, VEGF expression associated with concomitant tumor necrosis may help identify renal cell carcinomas susceptible to antiangiogenic therapy.
Effects of Helicobacter pylori and bile on N-methyl-N′-nitro-N′-nitrosoguanidine exposed antral mucosa of C57BL/6 miceLoogna, Peter; Franzén, Lennart; Sipponen, Pentti; Domellöf, Lennart
doi: 10.1007/s004280100456pmid: 11764387
The aim of this study was to evaluate the early influence of Helicobacter pylori infection on cell kinetics in the antral mucosa of mice exposed to N-methyl-N′-nitro-N′-nitrosoguanidine (MNNG) and bile alone or in combinations. Four hundred and one C57BL/6 male and female mice were assigned into seven treatment groups and one non-treated control group. The gastric antrums were assessed by histology and immunohistochemistry for studies of cell proliferation and apoptosis at 32 and 44 weeks. One female and one male mouse had developed dysplastic adenomas in the pylorus mucosa and one male animal had dysplastic proliferation in the antrum. Only one of these lesions occurred in a H. pylori colonized animal. H. pylori infection significantly increased the cell proliferation at 32 weeks and promoted the cell proliferation in the MNNG and bile group at 44 weeks. Female mice showed less increase in cell proliferation than did the males. No change in apoptosis was seen in any of the groups. Bile had no promotional effect on cell proliferation. These results indicate that H. pylori infection has the potential to alter epithelial cell kinetics as well as antrum mucosa of an animal species that is regarded as resistant to MNNG. However, this change is not sufficient to promote the early development of neoplastic lesions.
Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritisRinaldi, N.; Willhauck, M.; Weis, D.; Brado, B.; Kern, P.; Lukoschek, M.; Schwarz-Eywill, M.; Barth, T.
doi: 10.1007/s004280100432pmid: 11764389
Collagen type IV is a structural matrix protein which contributes to the structural organization of the synovia. In order to characterize the distribution of this protein in synovia with chronic synovitis, collagen type IV was detected by immunochemistry in normal synovia and in synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). A decrease of collagen type IV was observed in synovial layers of rheumatoid synovia, which statistically correlated with the grade of inflammation and with the thickness of the synovial layer. In vitro, we found no differences in the gene expression of collagen type IV in cultures of fibroblast-like synoviocytes (FLS) derived from OA and RA using a reverse-transcriptase polymerase chain reaction. Nevertheless, we observed a downregulating effect of tumor necrosis factor-α and interleukin (IL)-1β on the gene expression of collagen type IV only in FLS isolated from patients with RA. The effect of IL-1β was dose dependent. In summary, we observed an inflammation-associated decrease of collagen type IV in the synovial layer of rheumatoid synovia. Inflammatory cytokines may play a role in regulating the synthesis of collagen type IV in the rheumatoid process in vivo.