Imatinib-associated pulmonary alveolar proteinosis.
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Adult↗
Biomedical subjects
Roland Moll
Publications and source records attributed to Roland Moll.
CD34+ fibrocytes in tubular carcinomas and radial scars of the breast.
The present study was undertaken to analyze whether and to what extent CD34+ fibrocytes and alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts occur in the stroma of radial scars and tubular carcinoma of the breast. We investigated a total of 24 radial scars obtained from 23 females and a total of 43 tubular carcinomas. All tubular carcinomas showed a virtually complete loss of CD34+ fibrocytes paralleled by a gain of alpha-SMA-positive myofibroblasts. The peripheral parts of radial scars harbored CD34+ fibrocytes comparable to normal breast tissue. In 23 of 24 radial scars, the central core was characterized by a loss of CD34+ fibrocytes accompanied by the presence of alpha-SMA-positive myofibroblasts in six cases, a pattern that up to now has only been described in malignant breast lesions. This finding underlines the close relationship between tubular carcinomas and radial scars. We conclude CD34- and alpha-SMA immunohistochemistry to be valuable adjunctive tools in distinguishing radial scars from tubular carcinomas. In the present study, the presence of CD34+ fibrocytes excluded malignancy. The absence of CD34+ fibrocytes paralleled by the presence of alpha-SMA myofibroblasts indicated malignancy in most cases, although it has to be carefully considered that in a minority of cases (6 of 24) the central core of radial scars may disclose this stromal composition.
Actins↗
Images in cardiovascular medicine. Unusual manifestation of Libman-Sacks endocarditis in systemic lupus erythematosus.
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Adult↗
Tight junction-related structures in the absence of a lumen: occludin, claudins and tight junction plaque proteins in densely packed cell formations of stratified epithelia and squamous cell carcinomas.
Tight junctions (TJs), hallmark structures of one-layered epithelia and of endothelia, are of central biological importance as intramembranous "fences" and as hydrophobic "barriers" between lumina represented by liquid- or gas-filled spaces on the one hand and the mesenchymal space on the other. They have long been thought to be absent from stratified epithelia. Recently, however, constitutive TJ proteins and TJ-related structures have also been identified in squamous stratified epithelia, including the epidermis, where they occur in special positions, most prominently in the uppermost living epidermal cell layer, the stratum granulosum. Much to our surprise, however, we have now also discovered several major TJ proteins (claudins 1 and 4, occludin, cingulin, symplekin, protein ZO-1) and TJ-related structures in specific positions of formations of epithelium-derived tissues that lack any lumen and do not border on luminal or body surfaces. Using immunohistochemistry and electron microscopy we have localized TJ proteins and structures in peripheral cells of the Hassall's corpuscles of human and bovine thymi as well as in specific central formations of tumor nests in squamous cell carcinomas, including the so-called "horn pearls". Such structures have even been found in carcinoma metastases. In carcinomas, they often seem to separate certain tumor regions from others or from stroma. The structural significance and the possible functional relevance of the locally restricted synthesis of TJ proteins and of the formations of TJ-related structures are discussed. It is proposed to include the determination of the presence or absence of such proteins and structures in the diagnostic program of tumor pathology.
Animals↗
Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma.
Transport proteins mediating the selective uptake of organic anions into human hepatocytes include the organic anion transporters SLC21A6 (also termed OATP2, OATP-C, or LST-1) and SLC21A8 (OATP8). Both transporters are localized to the basolateral membrane of human hepatocytes. Because of the importance of these transporters for hepatobiliary elimination, including the removal of bilirubin and its conjugates from the blood circulation, we have generated monoclonal antibodies for studies on the expression and localization of these transport proteins. We describe two antibodies, designated monoclonal antibody MDQ (mMDQ) and monoclonal antibody ESL (mESL), directed against the amino terminus and the carboxyl terminus of human SLC21A6, respectively. Both antibodies have been characterized by immunoblot analysis, immunoprecipitation, and immunofluorescence microscopy. While mESL reacted specifically with SLC21A6, mMDQ detects both SLC21A6 and SLC21A8. Neither of the two antibodies reacted with other human, or with dog, rat, or mouse liver SLC21A family members. Antibody mMDQ may be used for the simultaneous detection of SLC21A6 and SLC21A8 in immunoblotting because of its immunoreactivity with both molecules and because of the different molecular masses of both glycosylated proteins in human hepatocytes. This is exemplified in hepatocellular carcinomas where SLC21A6 and SLC21A8 were differentially synthesized and showed an irregular staining pattern. Both transport proteins have not been detected in human hepatoma HepG2 cells. In routine paraffin sections, 10 of 12 hepatocellular carcinomas were focally positive with antibody mMDQ. In contrast, cholangiocarcinomas and liver metastases of colorectal and pancreatic adenocarcinoma were negative without exception. This suggests the usefulness of SLC21A6/SLC21A8 within a panel of tumor markers for hepatocellular carcinomas. Moreover, both antibodies should be useful in studies on the expression and localization of two important uptake transporters of human hepatocytes under physiologic and pathophysiologic conditions.
Adenocarcinoma↗
[Traumatic subarachnoid-pleural fistula causing tension pneumocephalus].
Uncommon subarachnoid-pleural fistula can be caused by a blunt or penetrating trauma and can also occur after a thoracal or neurosurgical operation, ending to a progredient pneumocephalus. Clinical findings might be an enlarging tension pneumocephalus without a cranial fracture, but in most times they will be overlayed by other accompanied injuries, neurologic symptoms can dominate, also rapidly filling clear pleural effusions with obscure cause. Oppurtune identification of the reason of the pneumocephalus and mostly early surgical intervention prevent neurological deficit, CNS infection and other complications.
Diagnosis, Differential↗
CD34(+) fibrocytes in normal cervical stroma, cervical intraepithelial neoplasia III, and invasive squamous cell carcinoma of the cervix uteri.
CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix.
Adult↗
Images in cardiovascular medicine. Phenotype of infiltrating T lymphocytes in cardiac sarcoidosis.
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Adult↗
Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ.
Current classification systems in proliferative mammary gland pathology are based on a two-cell system, recognizing only glandular and myoepithelial lines of differentiation. A third cell type has recently been characterized in normal breast tissue by double-immunofluorescence analysis to express cytokeratin 5 (Ck5) only. These cells were shown to represent progenitor or adult stem cells that give rise to the glandular and myoepithelial cell lineage. The double-labelling technique has been applied to characterize a spectrum of intraductal epithelial proliferations, namely benign usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ, all of which are thought to represent the gradual steps of a sequence in the development of breast cancer. Immunofluorescence studies with specific antibodies against Ck5, Ck8/18/19, and smooth muscle actin were complemented by western blotting analysis of Ck5 and Ck8/18/19 expression in normal breast tissue and in proliferative lesions. Usual ductal hyperplasia appears to be a Ck5-positive committed stem (progenitor) cell lesion with the same differentiation potential as seen in the normal breast. This is in sharp contrast to atypical ductal hyperplasia/ductal carcinoma in situ, which display the differentiated glandular immunophenotype (Ck8/18/19-positive, but Ck5-negative). These data require the abandonment of the idea of an obligate biological continuum of intraductal proliferations from benign to malignant. This study provides evidence that cells undergoing malignant transformation tend to be fairly advanced in the glandular lineage of differentiation. The committed stem (progenitor) cell model may contribute to a better understanding of both benign proliferative breast disease and breast cancer development.
Blotting, Western↗
CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions.
Besides its function as a matrix-producing cell, the CD34+ fibrocyte has been reported to be an antigen-presenting cell capable of priming naive T cells in situ. Therefore, it has been claimed that the CD34+ fibrocyte may play an important role in host response to tissue damage. The objective of the present study was to analyze the presence and distribution of CD34+ fibrocytes and smooth muscle actin (SMA) reactive myofibroblasts in relation to the underlying pancreatic disease. We investigated a total of 12 pancreatic adenocarcinomas, 7 endocrine tumors of the pancreas, and 8 cases of chronic pancreatitis; in 11 cases, normal pancreatic tissue was available. The stroma of normal pancreatic tissue harbored diffusely scattered CD34+ fibrocytes. Chronic pancreatitis was characterized by an increased number of stromal CD34+ fibrocytes paralleled by a gain of SMA reactive myofibroblasts which were not observed in the normal pancreatic stroma. The stroma of pancreatic ductal adenocarcinomas and endocrine tumors was devoid of CD34+ fibrocytes or showed at least a focal loss of this cell type, whereas SMA reactive myofibroblasts were detected in both endocrine tumors and adenocarcinomas. We conclude that detection of CD34+ fibrocytes may constitute an adjunctive tool in distinguishing chronic pancreatitis from ductal adenocarcinoma since the absence of this cell population strongly favors a neoplastic process. Moreover, CD34+ fibrocytes and myofibroblasts appear to be involved in stromal remodeling associated with chronic pancreatitis and ductal adenocarcinoma.
Actins↗
Intermediate-filament expression in ocular tissue.
Intermediate-filament proteins (IFPs) occur in the intracellular cytoskeleton of eukaryotic cells, and their expression in diverse tissues is related both to embryology as well as to differentiation. Although the available information concerning their functional properties in vivo is still incomplete, antibodies against individual IFPs are commonly used in immunohistochemical procedures as markers for differentiation, and these antibodies are of outstanding value in the routine histopathological evaluation of tumor specimens. This review presents a compilation of the currently available data concerning IFP expression in normal and diseased ocular tissues. Representatives of every known class of IFP have been detected in normal ocular tissues. The external epithelia exhibit complex expression patterns of cytokeratin (CK) polypeptides, with CK3 and CK12 being specific markers of the corneal epithelium. Recent research has revealed that single mutant CK polypeptides may play a role in the pathogenesis of corneal dystrophies. The internal ocular epithelia reveal simple but specific patterns of IFP expression, these comprising simple-epithelial CKs and/or the mesenchymal IFP, vimentin. The IFP complement of the neuronal structures of the eye embraces several distinct IFP classes and reflects the diversity of the cell types present at these sites. With respect to ocular tumors, the IFP profile of melanomas might be correlated with metastatic potential. In conclusion, IFP analysis may be able to cast light on the pathogenesis of ocular diseases, as well as being a valuable adjunct in ophthalmopathological diagnosis.
Animals↗
p16INK4a is a prognostic marker in resected ductal pancreatic cancer: an analysis of p16INK4a, p53, MDM2, an Rb.
OBJECTIVE: To identify the prognostic relevance of the G1/S cell cycle regulator genes p16INK4a, p53, MDM2, and Rb in patients with resected ductal pancreatic cancer (PC). SUMMARY BACKGROUND DATA: The tumor suppressor genes p16INK4a, p53, and Rb are altered in PC in 27% to 95%, 40% to 70%, and 5%, respectively. The role of MDM2 is not clearly defined in PC. The prognostic value of these cell cycle regulators has not been clarified. METHODS: Sixty-two patients with PC with complete follow-up who underwent potentially curative resections were included in the study. An extreme group analysis was performed including the 20 patients with the shortest survival and the 20 patients with the longest survival. Protein expression of p16, p53, MDM2, and Rb was investigated, and mutation analysis of p16INK4a and p53 was performed. p16INK4a promoter hypermethylation was examined by methylation-specific polymerase chain reaction. RESULTS: Significantly more tumors in the shortest-surviving patients had p16INK4a alterations compared with tumors of the longest-surviving patients. In contrast, the frequency of p53 alterations was not significantly higher in the shortest-surviving versus the longest-surviving groups. Stabilization of MDM2 and loss of Rb expression were identified in a minority of tumors, independent of survival length. CONCLUSIONS: The presence of p16INK4a alterations in resected tumors of patients with PC is connected with a worse prognosis, indicating patients that might benefit from adjuvant therapy regimens. p53 alterations, MDM2 overexpression, and loss of Rb expression could not be identified as prognostic markers from this study, but a larger study with greater statistical power might show a different result with regard to p53.
Biomarkers, Tumor↗
Mature cystic teratoma of the ovary with struma and benign Brenner tumor: a case report with immunohistochemical characterization.
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Brenner Tumor↗
Common adult stem cells in the human breast give rise to glandular and myoepithelial cell lineages: a new cell biological concept.
Breast biology and pathology are currently shaped by the two-cell concept that recognizes only glandular and myoepithelial cells. In the present study, we have visualized a previously unidentified cell population within the epithelial compartment of the breast, which displays the phenotypic characteristics of a committed stem cell. Immunofluorescence double labeling with digital image processing and Western blotting were applied to normal breast tissue as well as to noninvasive and invasive breast cancers using antibodies to basal cytokeratin 5 (Ck5), glandular cytokeratins 8/18 (Ck8/18/19), and smooth muscle alpha-actin (SMA) as markers for myoepithelial cells (SMA). A distinct population of cells was identified that expressed Ck5 in the absence of Ck8/18/19 or SMA. These cells differentiate toward glandular epithelial or myoepithelial Ck5-negative end cells passing through either Ck5/Ck8/18/19 or Ck5/SMA-positive intermediates. Our experiments clearly demonstrate a precursor or committed stem cell function of the Ck5-positive cell that is responsible for regeneration of the human adult breast epithelium. However, the observation that the vast majority of breast cancers display the glandular epithelial immunophenotype strongly suggests that the neoplastic cells derive from a late stage of the glandular epithelial differentiation pathway. The significance of this new cell biological model is that it might serve as a tool to unravel the regulatory mechanisms that govern regeneration and abnormal proliferation of breast epithelium at the cellular level.
Actins↗
CD34+ fibrocytes in invasive ductal carcinoma, ductal carcinoma in situ, and benign breast lesions.
The present study was undertaken in order to elucidate the question of whether the distribution of stromal CD34+ fibrocytes and smooth muscle actin (SMA)-reactive myofibroblasts differs between benign and malignant lesions of the breast. We investigated a total of 31 ductal carcinomas and 27 specimens with benign lesions of the breast (ductal hyperplasia, sclerosing adenosis, fibroadenoma, phyllodes tumor) and compared the distribution of CD34+ fibrocytes and SMA-reactive myofibroblasts. The stroma of normal breast tissue contained CD34+ fibrocytes, whereas SMA-reactive myofibroblasts were absent. All benign breast lesions exhibited stromal CD34+ fibrocytes and few lesions (fibroadenomas and phyllodes tumor) showed additional SMA-reactive myofibroblasts. In invasive breast cancer the stroma was devoid of CD34+ fibrocytes but a varying number of stromal SMA-reactive myofibroblasts was detectable. In the setting of the present study the loss of CD34+ fibrocytes was specific for invasive breast cancer and ductal carcinoma in situ, whereas SMA-reactive myofibroblasts were observed in different benign and malignant lesions. These findings may be helpful tools in distinguishing benign breast lesions (e.g., sclerosing adenosis) from invasive breast cancer and in characterizing stromal remodeling associated with invasive cancer.
Actins↗