elastin and Adenocarcinoma

To assess whether size, diameter, and large vein involvement of MR-detected extramural venous invasion (MR-EMVI) have an impact on neoadjuvant therapy response in rectal adenocarcinoma.. 57 patients with locally advanced rectal adenocarcinoma scanned with MRI before and after neoadjuvant therapy were included. Two abdominal radiologists evaluated the images with special emphasis on EMVI, on initial staging and after neoadjuvant treatment. The sensitivity and specificity of MRI for detection of rest EMVI were determined. The association of various MR-EMVI characteristics including number, size, and main vein involvement with treatment response was investigated. In subjects with discordance of radiology and pathology, elastin stain was performed, and images and slides were re-evaluated on site with a multidisciplinary approach.. At initial evaluation, 17 patients were MR-EMVI negative (29.8%) and 40 were MR-EMVI positive (70.2%). Complete/near-complete responders had less number (mean 1.45) and smaller diameter of MR-EMVI (mean 1.8 mm), when compared with partial responders (2.54 and 3.3 mm; p < 0.005). The sensitivity of MRI for rest EMVI detection was high, specificity was moderate, and in one patient elastin stain changed the final decision. In five patients with rest MR-EMVI positivity, carcinoma histopathologically had a distinctive serpiginous perivascular spread, growing along the track of vascular bundle, although it did not appear in intravascular spaces.. This study demonstrates that not only the presence, but also size and number of EMVI that may be significant clinically and thus these parameters also ought to be incorporated to the MRI evaluation and prognostication of treatment response. From pathology perspective, tumors growing alongside major vessels may also reflect EMVI even if they are not demonstrably "intravascular."

Topics: Adenocarcinoma; Biomarkers; Elastin; Humans; Magnetic Resonance Imaging; Neoadjuvant Therapy; Neoplasm Invasiveness; Rare Diseases; Rectal Neoplasms; Retrospective Studies

The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens.. We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used.. There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001).. We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calmodulin-Binding Proteins; Colorectal Neoplasms; Desmin; Elastin; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neovascularization, Pathologic; Pancreatic Neoplasms; Staining and Labeling; Stomach Neoplasms; Young Adult

During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for antibody generation and developed an ELISA assay (EL-NE) for the quantification of NE-degraded elastin.. Monoclonal antibodies were developed against 10 NE-specific cleavage sites on elastin. One EL-NE assay was tested for analyte stability, linearity and intra- and inter-assay variation. The NE specificity was demonstrated using elastin cleaved in vitro with matrix metalloproteinases (MMPs), cathepsin G (CatG), NE and intact elastin. Clinical relevance was assessed by measuring levels of NE-generated elastin fragments in serum of patients diagnosed with idiopathic pulmonary fibrosis (IPF, n = 10) or lung cancer (n = 40).. Analyte recovery of EL-NE for human serum was between 85% and 104%, the analyte was stable for four freeze/thaw cycles and after 24 h storage at 4°C. EL-NE was specific for NE-degraded elastin. Levels of NE-generated elastin fragments for elastin incubated in the presence of NE were 900% to 4700% higher than those seen with CatG or MMP incubation or in intact elastin. Serum levels of NE-generated elastin fragments were significantly increased in patients with IPF (137%, p = 0.002) and in patients with lung cancer (510%, p < 0.001) compared with age- and sex-matched controls.. The EL-NE assay was specific for NE-degraded elastin. The EL-NE assay was able to specifically quantify NE-degraded elastin in serum. Serum levels of NE-degraded elastin might be used to detect excessive lung tissue degradation in lung cancer and IPF.

Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Case-Control Studies; Elastin; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Female; Humans; Idiopathic Pulmonary Fibrosis; Leukocyte Elastase; Lung; Lung Neoplasms; Male; Middle Aged; Peptide Fragments; Small Cell Lung Carcinoma

The American Joint Committee on Cancer's Cancer Staging Manual 7th edition defines pericolonic tumor deposits (TDs) as discrete tumor foci in pericolic fat showing no evidence of residual lymph node (LN). This definition relies on subjective features rather than size (5th edition) or shape (6th edition) and introduced the category N1c. Although typically straightforward, metastases are encountered for which the distinction between LNs and TDs is unclear. For data to be meaningful, agreement on distinguishing features between positive LNs and TDs is needed.. To assess agreement among gastrointestinal pathologists evaluating difficult metastases and to report the distinguishing features they found helpful.. Twenty-five tumor metastases from right-sided colonic adenocarcinomas were selected in which the distinction between positive LNs and TDs was challenging. Virtual slides were reviewed by 7 gastrointestinal pathologists. A list of features potentially helpful in differentiating positive LNs and TDs was ranked for usefulness by each pathologist. Every metastasis was diagnosed as positive LN or TD. For each case diagnosed as positive LN, reviewers were asked to list every feature used in diagnosis.. Complete agreement was found for 11 of 25 metastases, 5 positive LNs and 6 TDs (κ statistic, 0.48; 95% confidence interval, 0.28-0.67). Top-ranked features included round shape, peripheral lymphocyte rim, peripheral lymphoid follicles, possible subcapsular sinus, residual LN in surrounding fibroadipose tissue, and thick capsule. The top used features were similar among reviewers.. Significant agreement on positive LNs and TDs in difficult colonic adenocarcinoma metastases was found among evaluators, but inconsistency remains. Round shape, peripheral lymphocyte rim, peripheral lymphoid follicles, possible subcapsular sinus, residual LN in surrounding fibroadipose tissue, and thick capsule were most often used to aid in diagnosis.

Topics: Adenocarcinoma; Adipose Tissue; Colonic Neoplasms; Diagnosis, Differential; Elastin; Humans; Lymph Nodes; Lymphatic Metastasis; Lymphocytes; Observer Variation; Prognosis; Retrospective Studies

Surgical removal and pathologic handling of lung tissue has a compressive effect upon its architecture. The effect of surgical atelectasis on morphology has not been examined in depth, especially with respect to lung adenocarcinomas.. To examine the influence of surgical atelectasis on morphologic lepidic growth pattern, mimicking papillary adenocarcinoma pattern.. In 2 cases serial sections of resected pulmonary adenocarcinoma were used, as was a 3-dimensional reconstruction. Elastin stains were performed on primary and metastatic adenocarcinomas.. Perfusion fixation of another case showed marked morphologic differences of less compressed peripheral lung tissue, emphasizing the preexisting alveolar structure. An elastic stain may help identify true lesional architecture.. We demonstrate that microscopic sections of adenocarcinoma in situ in compressed/collapsed tissue may give rise to a pseudopapillary pattern mimicking invasive adenocarcinoma. Accurate appreciation of different tumor architecture in lung adenocarcinoma has important biologic and clinical implications. Pathologists should be aware of the possibility of misclassification of adenocarcinoma pattern due to tissue artifacts caused by lung tissue handling.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Aged, 80 and over; Artifacts; Biomarkers, Tumor; Diagnosis, Differential; Elastin; Female; Histocytochemistry; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Specimen Handling; Tomography, X-Ray Computed

Venous invasion (VI) is an independent prognostic indicator in colorectal cancer and may prompt consideration for adjuvant chemotherapy in patients with stage II tumors. Recent evidence suggests that VI is underreported in colorectal cancer and that detection may be enhanced by an elastin stain. This study aimed (1) to determine the impact of an elastin stain on VI detection and on interobserver agreement between gastrointestinal (GI) and non-GI pathologists, and (2) to identify factors associated with increased VI detection. Forty hematoxylin and eosin (H&E)-stained slides were circulated to 6 GI and 6 non-GI pathologists who independently assessed the VI status as positive, negative, or equivocal. Six weeks later, 40 corresponding Movat-stained slides were recirculated together with the original H&E slides and reassessed for VI status. Detection of VI was >2-fold higher with a Movat stain compared with an H&E stain alone (46.4% vs. 19.6%, P=0.001). GI pathologists detected VI more frequently than non-GI pathologists on both H&E (30.0% vs. 9.2%, P=0.029) and Movat (58.3% vs. 34.6%, P=0.018) stains. There was higher interobserver agreement in the case of a Movat stain, particularly for extramural VI (H&E: κ=0.23 vs. Movat: κ=0.41). A poststudy survey indicated that GI pathologists and non-GI pathologists applied similar diagnostic criteria but that GI pathologists more frequently applied "orphan arteriole" and "protruding tongue" signs as diagnostic clues to VI. This study confirms that VI is underdetected on H&E and highlights the role of elastin staining in improving VI detection and interobserver agreement. Strategies to improve VI detection are warranted.

Topics: Adenocarcinoma; Biomarkers, Tumor; Colorectal Neoplasms; Elastin; False Positive Reactions; Gastroenterology; Humans; Neoplasm Invasiveness; Neoplasm Staging; Observer Variation; Pathology, Surgical; Predictive Value of Tests; Prognosis; Reproducibility of Results; Staining and Labeling; Vascular Neoplasms; Veins

Ovarian cancer has an extremely high mortality rate resulting from poor understanding of the disease. In order to aid understanding of disease etiology and progression, we identify the endogenous fluorophores present in a mouse model of ovarian cancer and describe changes in fluorophore abundance and distribution with age and disease.. A mouse model of ovarian cancer was created by dosing with 4-vinylcyclohexene diepoxide, which induces follicular apoptosis (simulating menopause), and 7,12-dimethylbenz[a]anthracene, a known carcinogen. Imaging of ovarian tissue was completed ex vivo with a multiphoton microscope using excitation wavelength of 780 nm and emission collection from 405 to 505 nm. Two-photon excited fluorescence images and corresponding histologic sections with selective stains were used to identify endogenous fluorophores.. The majority of collected fluorescence emission was attributed to NADH and lipofuscin, with additional contributions from collagen and elastin. Dim cellular fluorescence from NADH did not show observable changes with age. Changes in ovarian morphology with disease development frequently caused increased fluorescence contributions from collagen and adipose tissue-associated NADH. Lipofuscin fluorescence was much brighter than NADH fluorescence and increased as a function of both age and disease.. Our finding of NADH fluorescence patterns similar to that seen previously in human ovary, combined with the observation of lipofuscin accumulation with age and disease also seen in human organs, suggests that the findings from this model may be relevant to human ovarian disease. Increased lipofuscin fluorescence might be used as an indicator of disease in the ovary and this finding warrants further study.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Aging; Animals; Biomarkers, Tumor; Collagen; Cyclohexenes; Disease Progression; Elastin; Female; Image Interpretation, Computer-Assisted; Linear Models; Lipofuscin; Mice; Microscopy, Fluorescence, Multiphoton; NAD; Ovarian Neoplasms; Ovary; Vinyl Compounds

Elastin-rich lung extracellular matrix is largely remodeled during tumor invasion. Elastin degradation produces peptides displaying a wide range of biological activities. These elastin derived peptides (EP) interact with the elastin receptor complex (ERC) but also bind to α(V)β(3) integrin and galectin-3. In this study, we explored the role of EP and their receptors in tumor progression of lung carcinomas. Non-invasive and invasive lung tumor cell lines were incubated in presence of kappa-elastin (κE) or with synthetic peptides displaying receptor-specific sequences (VGVAPG, GRKRK, AGVPGLGVG and AGVPGFGAG). Modified Boyden chamber assays revealed an increased invasive capacity of invasive cells induced by κE. EP treatment had no effect on cell proliferation but zymography analysis revealed an increase of pro-MMP-2 and uPA levels in the conditioned media of treated cells. Moreover, the active form of MMP-2 was increased in invasive cells. Interestingly, this regulation was not observed at the mRNA level and actinomycin D was unable to inhibit κE effects. We also observed that the regulation of proteases protein level following κE treatment was an early process detectable after 1 h. All these effects could not be inhibited by lactose and V14, two ERC antagonists, or by blocking antibodies against α(V)β(3) integrin and galectin-3. Finally, VGVAPG and GRKRK failed to reproduce κE effects whereas nonapeptides partially mimicked them. These results demonstrate that treatment with EP up-regulates invasiveness of lung tumor cells via the release of proteolytic enzymes. This modulation involves post-transcriptional mechanisms and a nonapeptide-receptor different from the ERC, α(V)β(3) integrin and galectin-3.

Topics: Adenocarcinoma; Biomarkers, Tumor; Blotting, Western; Cell Movement; Cell Proliferation; Elastin; Extracellular Matrix; Galectin 3; Gene Expression Profiling; Humans; Integrin alphaVbeta3; Lung Neoplasms; Matrix Metalloproteinase 2; Oligonucleotide Array Sequence Analysis; Oligopeptides; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing, Post-Transcriptional; RNA, Messenger; Urokinase-Type Plasminogen Activator

Autofluoresence can be used to detect neoplasia in the colon. Two known fluorophores, collagen and elastin, are probably partly responsible for colonic emission spectra. Their contribution to colonic autofluorescence was investigated.. Autofluorescence spectra of normal, dysplastic, and malignant colonic tissue were studied by using excitation wavelengths from 280 nm to 350 nm. The wavelengths of peak emission and their widths at half maximum intensity were measured. Similar measurements were performed on collagen types I, III, IV, V, IX, and elastin. Colonic spectra were compared to those of collagen and elastin. Spectral differences between collagen types IV (basement membrane) I, III, V, and IX were studied.. Four major emission peaks were noted whose wavelength of peak emission and full widths at half maximum intensity were independent of tissue histology. The emission spectra of type IV collagen differed markedly from that of nonbasement membrane collagens and elastin.. Type IV (basement membrane) collagen is most likely responsible for the emission peak at 365 nm. The spectra of basement membrane collagen and not other types of collagen should be used in studies of epithelial tissue spectra. Elastin did not appear to be responsible for any of the four autofluorescence peaks observed in colonic tissue.

Topics: Adenocarcinoma; Adenoma; Adenomatous Polyps; Basement Membrane; Collagen; Colon; Colonic Neoplasms; Elastin; Humans; Intestinal Mucosa; Spectrometry, Fluorescence

Clinically aggressive neoplastic development appears to be associated with extensive extracellular matrix biosynthesis. Collagen, non-collagenous protein and elastin from 21 specimens of benign hypertrophic prostate (BPH) and 15 samples of cancerous prostate were determined. Collagen and non-collagenous protein concentrations of BPH were similar to those in prostatic carcinoma. The elastin concentration of well or moderately differentiated prostatic carcinoma was greater than that in BPH specimens. These results may provide an explanation as to the early antecedent or possible aetiology of prostatic carcinoma.

Topics: Adenocarcinoma; Aged; Collagen; Connective Tissue; Elastin; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Elastin metabolism parameters (elastin-derived peptides and elastase-like activity) were determined in sera of patients with lung cancer and in healthy controls. The concentration of elastin-derived peptides was statistically significantly elevated in the lung cancer group. There was no statistically significant difference in the serum elastase-like activity between the groups studied. These data seem to indicate an enhanced metabolism of elastin in patients with lung cancer.

Topics: Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Elastin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pancreatic Elastase; Peptide Fragments

The aim of this study was to investigate anti-elastin antibodies of the IgG and IgM types in sera of patients suffering from lung cancer, using the DOT immunobinding assay. We studied 96 pathological and 40 control sera. Anti-elastin antibodies were found to be present in 45% of patients with small cell lung cancer, 19% of subjects with adenocarcinoma and not-identified lung tumor and 15% of patients with squamous cell lung cancer. They circulated in 5% of control persons only. The highest values of their titers were observed in the advanced stages of disease. In 55% of anti-elastin antibody positive small cell lung cancer patients, antibodies were of the IgM type, suggesting the initial step of the autoimmunization to elastin.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Elastin; Female; Humans; Immunoblotting; Immunoglobulin G; Immunoglobulin M; Lung Neoplasms; Male; Middle Aged

Cancer cell motility has been associated with metastatic potential of sublines of the Dunning R-3227 rat prostatic adenocarcinoma model. However, three sublines of high motility lacked the capacity for metastasis. In all previous works, motility has been studied upon plastic and only upon attached cells at least 18 h after gravity plating. We studied two highly motile sublines; MAT-LyLu metastasizes to lungs and lymph nodes whereas PIF-1 metastasizes rarely. We compared the motility and attachment capability of cells from the Dunning model in serum-free media upon plastic, glass, laminin, type IV collagen, fibronectin, and elastin to determine whether study upon more physiological surfaces could better explain the discrepancy in metastatic capability observed in vivo. In the high-motility low-metastatic PIF-1 and high-motility high-metastatic MAT-Lylu sublines, membrane ruffling, pseudopodal extension, and cellular translation upon plastic in serum-free media were reduced (P less than 0.0001) by 33 and 31, 70 and 60, and 77 and 65%, respectively. When returned to serum-containing media, biological characteristics (histology, chromosomal number, growth rate, host survival, and metastatic potential) were unchanged. Motility was affected by substrate (analysis of variance, P less than 0.05); however, no consistent pattern of enhancement or detriment occurred in any substrate across both sublines. When motility was compared between sublines, membrane ruffling and cellular translation were relatively unaffected by substrate, whereas pseudopodal extension was altered significantly by different substrates. However, upon individual substrates, no significant differences in motility existed between the two sublines to resolve the inconsistency of high-motility but low-metastatic potential in the PIF-1 subline. Therefore, we examined cell attachment, since in order for a metastatic cell to be motile upon substrate, it must first attach to it. Percentage of 10(5) cells attached was determined in serum-free media with the use of a cell counter after 1, 2, 4, 8, and 16 h on plastic and plastic coated with laminin, fibronectin, elastin, or type IV collagen. Cell attachment increased with time (P less than 0.05) on all substrates for MAT-LyLu (r = 0.95) and PIF-1 (r = 0.98). Attachment of MAT-LyLu cells was impaired by fibronectin and enhanced by elastin, laminin, and type IV collagen compared to plastic at all time points.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adenocarcinoma; Animals; Cell Adhesion; Cell Movement; Collagen; Culture Media, Serum-Free; Elastin; Fibronectins; Laminin; Male; Neoplasm Metastasis; Prostatic Neoplasms; Rats; Tumor Cells, Cultured