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Apocrine epithelium of the breast: does it result from metaplasia?

Benign and malignant breast lesions may show an apocrine epithelium considered to be the result of metaplasia. In an attempt to clarify the histogenesis of the breast apocrine epithelium we searched for the presence of apocrine cells or cells with apocrine differentiation during human breast development. We analysed 10 autopsy specimens of female breasts from fetuses between 28 and 40 weeks of gestational age and tissue from 6 normal breasts, obtained after breast reduction in nulliparous young women between 22 and 28 years of age. Formalin-fixed, paraffin-embedded sections were stained with haematoxylin-eosin, PAS-diastase and a monoclonal antibody (BRST-2) anti-GCDFP-15, which is a specific apocrine marker. A 40-week fetal breast was analysed by electron microscopy. No cells with histological and ultrastructural apocrine features were found in the ducts of fetal breasts. All fetal breasts showed some ducts with sparse GCDFP-15-immunoreactive cells; the number of these cells increased with gestational age. PAS-diastase was negative. No cells with apocrine morphology were found in ducts and lobules of normal adult breasts. Scattered GCDFP-15-positive luminal epithelial cells and rare PAS-diastase-positive cells were observed in some lobules of all adult breasts. Cells with biochemical characteristics (GCDFP-15 expression) of apocrine differentiation are evident during human fetal breast development and persist in adult mammary glands. Unknown stimuli may induce these cells to take on an apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than metaplasia. We suggest the term "apocrine differentiation precursor cells" for GCDFP-15-positive breast epithelial cells with no apocrine morphology.

Adult↗

A morphogenetic concept of salivary duct regeneration and metaplasia.

The exact mechanisms of physiological regeneration and of metaplastic processes of the salivary duct have not been definitely established, although regeneration from a putative uncommitted stem cell population has long been favored. In the present study, double immunohistochemical labeling for Ki 67 and alpha-actin or different cytokeratin subtypes, respectively, made possible an exact localization and quantification of cellular proliferation in the regular salivary duct and in different types of metaplasia. Our data demonstrate a baseline proliferative capacity in all five cell types of the salivary duct. Luminal secretory cells of the acinus and intercalated duct regenerate independently from myoepithelial or basal cells. In contrast, the renewal of oxyphilic cells in the striated and excretory duct is maintained by proliferation and differentiation of basal cells. The great majority of metaplasias develops from uncommitted, Bcl-2 positive basal cells of striated/excretory ducts which possess an enormous capacity for pluridirectional morphogenetic differentiation. Despite this important role of basal cells, our findings demonstrate that all cell types principally have to be considered as potential progenitor cells for salivary gland tumors. The improved insight into regenerative and metaplastic processes of the salivary duct may contribute to a better understanding of the complex formal carcinogenesis.

Actins↗

The Z-line appearance and prevalence of intestinal metaplasia among patients without symptoms or endoscopical signs indicating gastroesophageal reflux.

BACKGROUND: A four-graded classification of the Z-line appearance (ZAP) has been proposed, which was shown to correlate with the prevalence of intestinal metaplasia (IM) among patients with gastroesophageal reflux disease (GERD). The aim of this study was to determine the ZAP grade and the prevalence of IM among patients without GERD. METHODS: In this study, 53 consecutive patients without signs or symptoms of GERD were included. RESULTS: A normal Z-line (ZAP grade 0) was found in 26 patients (51%), and this group had a lower prevalence of Helicobacter pylori infection and atrophy in the cardia than ZAP grade patients. The non-GERD patients in this study had less ZAP pathology than the GERD patients in our previous study. Intestinal metaplasia at the Z-line, observed in 17% of the patients, was found to associate with peptic ulcer and carditis. CONCLUSION: The normal Z-line is feasibly defined as ZAP grade 0.

Adult↗

Pediatric chordoid glioma with chondroid metaplasia.

Chordoid gliomas are uncommon primary brain tumors that arise in the region of the third ventricle. Reports of this entity to date have been limited to adults. We present a case of a chordoid glioma arising in the hypothalamic/third ventricle region of a 12-year-old male who presented with visual symptoms. The neoplasm consisted of cords and clusters of well-differentiated, spindled-to-rounded cells containing abundant eosinophilic cytoplasm within a prominent mucinous matrix. Unlike other chordoid gliomas, this lesion contained islands and sheets showing cartilaginous differentiation intermixed with the glial component. A graded transition between neoplastic glial and chondroid regions was evident, and cells in both regions were strongly immunoreactive for GFAP and S-100. Cartilaginous metaplasia is infrequent in gliomas, but occurs most often in pediatric neoplasms of the midline such as this chordoid glioma. Thus, chondroid metaplasia represents an unusual histopathologic feature of chordoid glioma-in this case, presenting in a child.

Antigens, Nuclear↗

Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization.

Helicobacter pylori plays a causative role in the development of chronic atrophic gastritis, intestinal metaplasia (IM), and stomach cancer. Although IM has long attracted attention as a putative preneoplastic lesion for stomach cancers, its clinicopathologic significance has yet to be clarified in detail. Using gastric and intestinal epithelial cell markers, IM was here divided into two major types: a gastric-and-intestinal (GI) mixed type and a solely intestinal (I) type. In the former, gastric and intestinal phenotypic markers appeared not only at the glandular but also at the cellular level. Furthermore, neuroendocrine cells also showed intestinalization along with their exocrine counterparts. In animal models, GI-type IM was found to appear first, followed by the solely I type. Summarizing these data, it was suggested that IM might be caused by the gradual intestinalization of stem cells from the GI to the I type. The molecular mechanisms of IM include the ectopic expression of CDX1, CDX2, OCT-1, and members of the Erk pathway. Suppression of the expression of gastric transcription factors such as SOX2, genes that are involved in the Sonic hedgehog pathway, and RUNX3, a tumor suppressor gene, could be additional relevant alterations. The expression of PDX1 may also be associated with pseudopyloric gland metaplasia and IM. Detailed analysis of gene regulation may shed light on the molecular bases of gastric lesions, leading to strategies for chemoprevention.

Animals↗

Influence of cyclic hydrostatic pressure on fibrocartilaginous metaplasia of achilles tendon fibroblasts.

The goal of this study was to demonstrate whether cyclically imposed hydrostatic pressure, compressive in nature, could induce fibrocartilaginous metaplasia in a purely tendinous cell source in vitro. The effect of short-duration cyclic hydrostatic pressure on tendon fibroblasts (tenocytes) expanded from rat Achilles tendon was studied. Total RNA was isolated either immediately after loading or 24 h later. The mRNA expression of tendon and cartilage specific markers - Collagen types I and II, Sox9, and Aggrecan was quantified by real-time reverse transcription polymerase chain reaction over multiple biological samples (n=6). For immediately isolated RNA samples, there were statistically significant increases in mRNA expression of Aggrecan and Collagen type II, while Collagen type I significantly decreased. Noticeably, for RNA samples isolated 24 h later, there were further increases in mRNA expression of Aggrecan and Collagen type II, whereas Collagen type I increased roughly three-fold relative to the non-loaded control. These findings support the hypothesis that cyclic hydrostatic pressurization can induce fibrocartilaginous metaplasia in tenocytes by upregulation of cartilaginous gene expression. Also, it was demonstrated that changes in mRNA expression as a result of single 2 h pressurization persist even up to 24 h.

Achilles Tendon↗

Use of methylene blue for detection of specialized intestinal metaplasia in GERD patients presenting for screening upper endoscopy.

The ability of randomly obtained biopsy specimens to identify intestinal metaplasia in the distal esophagus is low. Use of vital staining has been suggested, as stains are taken up by areas histologically identified as specialized intestinal metaplasia (SIM). This study evaluated the role of methylene blue (MB) staining for identification of SIM in GERD patients undergoing a screening endoscopy. Chromoendoscopy of the distal esophagus using 1% MB was performed on 52 GERD patients presenting for their first endoscopy. Biopsies were obtained from areas that were stained darkly, stained lightly, unstained, or macroscopically abnormal. In patients with no MB staining, four-quadrant biopsy of the distal esophagus was performed. Twenty-seven patients (52%) showed staining with MB, while 25 patients did not. Two hundred sixty-six biopsies were obtained. SIM was detected in 11 (21%) subjects (SIM+) but not in the remaining 41 (SIM-). One hundred sixty-five biopsies were unstained (25 SIM+, 140 SIM-) and 101 were stained (12 SIM+, 89 SIM-). The per-biopsy sensitivity and specificity of MB for detection of SIM were 32.4 and 85%, while the per-patient sensitivity and specificity were 63.3 and 51.2%. MB staining for detection of SIM in GERD patients without a macroscopic appearance suggestive of a columnar-lined esophagus is a poor screening tool for SIM.

Adult↗

A reappraisal of the coelomic metaplasia theory by reviewing endometriosis occurring in unusual sites and instances.

Endometriosis occurring in unusual sites and instances was reviewed for the purpose of exploring the pathogenesis of the disease. Endometriosis is frequently observed in the pelves of menstruating women. It occurs in teenagers even before menarche, in women who have never menstruated, and in postmenopausal women. It affects not only the pelvic organs but also the right-sided thoracic organs and rarely the extremities. It occurs in men who are castrated and treated with estrogen. The affected sites in both common and uncommon endometriosis include cells arising from the coelomic membrane and sites exposed to metaplasia-inducing substances such as estrogen and unknown factors liberated from the degenerating endometrium. This appears to strengthen the coelomic metaplasia theory, although additional basic and experimental data must still be accumulated to confirm this theory.

Child↗

Chronic esophagitis and gastric metaplasia are frequent late complications of esophageal atresia.

Long-term follow-up examination with esophagogastroduodenoscopy was performed on 39 esophageal atresia patients 2 to 11 years (mean, 7.6) after the anastomotic operation. Nine of these patients had undergone fundoplication for symptomatic gastroesophageal reflux. The subjective results at the last follow-up were as follows: excellent in 25, good in 10, and fair in 4 patients. The endoscopic findings were normal in 17 patients. Endoscopy of the remaining 22 patients showed esophagitis in 20, 5 associated with Barrett's change. Hiatal hernia was found in 10 patients. The fundoplication was totally or partially disrupted in 3 patients. Esophageal biopsies were obtained from 37 patients. The histological findings were as follows: esophagitis in 21, gastric metaplasia in 3, and normal esophageal mucosa in 13 patients. The endoscopic and histological findings correlated poorly with subjective results as more than half of the patients with excellent subjective results had esophagitis, one of them with gastric metaplasia. Therefore, long-term endoscopic follow-up of all esophageal atresia patients is warranted.

Child↗

Cell-specific alterations in glycoconjugates in the development of squamous metaplasia induced by benzo[a]pyrene in hamster tracheal explants.

Squamous metaplasia of tracheal mucosa, putative preneoplastic lesions, involves replacement of normal mucociliary epithelium with epidermoid lesions. Alterations in cell differentiation and neoplasia accompany changes in glycoconjugates at the plasma membrane. Lectins which bind to specific cell surface glycoconjugates are used to elucidate such alterations. We have used peanut agglutinin (PNA) and concanavalin A (Con A) as specific molecular probes to elucidate cell specific alterations in the development and progression of squamous metaplasia in the hamster tracheal explants induced by benzo[a]pyrene (BP), a component of cigarette smoke. The tracheal explants were cultured in serum-free chemically defined medium and treated with BP (7.5 micrograms/ml) for up to 15 days. At this time, 80-90% of the carcinogen treated explants exhibited epidermoid lesions at various stages of development. The untreated control explants maintained normal pseudostratified epithelium. In these explants, PNA and Con A exhibited moderate reaction in the cytoplasm of luminal mucociliary cells; the basal cells showed no reaction. In early metaplastic lesions PNA and Con A stained only the cytoplasm of luminal cells; the metaplastic cells along the basal lamina were negative. In well-developed lesions, in which the luminal mucociliary layer was still intact overlying the lesions, the metaplastic epithelium remained unreactive with the lectins. In highly advanced lesions exhibiting cornification, and in which the mucociliary layer was sloughed, the metaplastic lesions showed strong reaction with both the lectins. The reaction was limited mainly to the plasma membrane of the metaplastic cells. These results show that induction and progression of the BP induced lesions accompany dynamic cell specific alterations in glycoconjugates. The epidermoid lesions acquire glycoconjugates rich in beta-D-galactose and D-mannose. These results are also consistent with the basal cell origin of the metaplastic lesions.

Animals↗

Detection of human papillomavirus DNA in squamous bronchial metaplasia and squamous cell carcinomas of the lung by in situ hybridization using biotinylated probes in paraffin-embedded specimens.

We examined a series of paraffin-embedded tissue specimens from 10 cases of squamous bronchial metaplasia and 33 cases of squamous cell carcinoma of the lung for histologic characteristics and for the presence and typing of human papillomavirus (HPV) by molecular in situ hybridization with biotinylated probes types 6, 11, 16 and 18 under stringent conditions (temperature, 19 degrees C). Fourteen of these lesions (32.5%) showed typical condylomatous histologic changes. Human papillomavirus DNA was present in seven (16%) specimens. Type 6 HPV DNA was detected in one of the squamous bronchial metaplasia cases. In six of the squamous cell carcinomas cases (18%), HPV DNA was identified (type 18, three cases; type 16, one case; type 11, one case; and type 6, one case); one of the squamous cell carcinoma specimens contained both HPV types 16 and 18. Our data confirm the presence of HPV DNA in squamous metaplastic bronchial mucosa and epidermoid lung carcinoma on paraffin-embedded tissues. This suggests that an HPV infection with benign or potentially oncogenic HPV types could be associated not only with genital tumors, but also with bronchial and lung tumors. The role of HPV DNA in the process of malignancy conversion is not yet known; HPV DNA could possibly be a cocarcinogenic factor. In situ hybridization with biotinylated probes is a useful and appropriate method of retrospective analysis of HPV DNA sequences in routinely paraffin-embedded lesions. It may be used to identify patients at risk of more serious or possibly malignant progression.

Biotin↗

Intestinal metaplasia and dysplasia of prostatic urethra secondary to stricture.

We report a case of intestinal metaplasia and dysplasia (villous adenoma) of the prostatic urethra secondary to stricture of the prostatic portion of the urethra and chronic inflammation. This sequence of events has previously been recognized in the urothelium of the bladder as a precursor of adenocarcinoma of intestinal type. Premalignant dysplasia of glandular type is rare in the urethra, as is adenocarcinoma, and this case suggests that the pathway to some adenocarcinomas of the urethra may be through intestinal metaplasia and dysplasia similar to the process recognized in the stomach, nose, and urinary bladder.

Adenoma↗

Retinoid reversal of squamous metaplasia in organ cultures of tracheas derived from hamsters fed on vitamin A-deficient diet.

Cytokinetic and ultrastructural studies were carried out to elucidate mechanisms involved in the reversal of squamous metaplasia (SM) by beta-retinoic acid in organ cultures of tracheas derived from vitamin A-deficient hamsters. Tracheal cultures exhibiting focal areas of SM were treated with the retinoid for up to 7 days. The retinoid significantly inhibited [3H]-thymidine labeling indices in the basal cells and stimulated the labeling indices in mucous cells. At the ultrastructural level the retinoid induced marked remodeling alterations in the metaplastic epithelium that included: (a) disruption of desmosomes and widening of intercellular spaces; (b) extensive vacuolation and degeneration of the metaplastic cells; (c) extrusion of the degenerated cells; (d) aggregation of keratin filaments; and (e) differentiation of certain basal cells into secretory cells. Consequently most degenerated metaplastic cells were extruded and the epithelium repopulated as a result of differentiation of basal cells into mucous cells and hyperplasia of the pre-existing mucous cells. The degenerative effects of the retinoid were limited to the metaplastic foci since the uninvolved epithelium adjoining metaplastic foci were not significantly altered. The results suggest that the restoration of normal tracheal epithelium following the retinoid treatment of explants exhibiting focal areas of squamous metaplasia is associated with the enhanced proliferation of the mucous cells. The inhibition of proliferation of basal cells further prevented hyperplasia and restored cell replication within the normal range.

Animals↗

A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum.

We have undertaken studies on carcinogenesis arising from precancerous lesions, such as squamous metaplasia and ulcerative lesions of the rat colorectum, after termination of degraded carrageenan administration. Rates of tumor incidence in groups that were given a 10% diet of degraded carrageenan for 2, 6 and 9 months were 5 rats out of 39 (12.8%), 8 out of 42 (19.0%) and 17 out of 42 (40.5%), respectively. The colorectal squamous metaplasia persisted in all rats and progressed irreversibly. Degraded carrageenan was deposited not only in the colorectal propria mucosa, but also in the other reticuloendothelial organs. These results show that, even with short-term degraded carrageenan administration, degraded carrageenan is carcinogenic to the colorectum of the rat after a prolonged period.

Animals↗

Ascorbic acid inhibits the squamous metaplasia that results from treatment of tracheal explants with asbestos or benzo[a]pyrene-coated asbestos.

Hamster tracheal explants were maintained in culture in the presence or absence of benzo[a]pyrene (BP), crocidolite asbestos, or BP-coated crocidolite. Dose-dependent squamous metaplasia was observed in the treated samples. L-Ascorbic acid and DL-alpha-tocopherol were able to partially protect the tracheal explants from the metaplastic response induced by crocidolite. Furthermore, ascorbic acid reduced the extent of metaplasia observed in hamster tracheal explants that were exposed to BP-crocidolite.

Animals↗

Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer.

Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of aneuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations.

Adult↗

A genetic locus of Helicobacter pylori inversely associated with gastric intestinal metaplasia.

The genomic contents of Helicobacter pylori strain C1 from a patient with gastric cancer and strain 98587 from a patient with duodenal ulcer disease were compared using a rapid subtractive hybridisation approach. A total of 11 tester-specific sequences representing gene specificity, DNA rearrangement and sequence variation were identified. This included two novel sequences, clone P32 and clone F5, which have no significant homologue in the database. H. pylori strains positive for clone P32 were less prevalent in patients with gastric intestinal metaplasia (12.5%) than in duodenal ulcer (39.1%) (p=0.036), or chronic gastritis (38.1%) (p=0.036). The results suggest that H. pylori clone P32 is potentially a useful marker for distinguishing intestinal metaplasia associated strains from others.

Amino Acid Sequence↗

Osseous metaplasia: case report and review.

OBJECTIVE: To discuss, through the experience of a case report and extensive literature review, the best practices for the diagnosis and treatment of osseous metaplasia, which is the cause of secondary infertility. DESIGN: Case report. SETTING: In vitro fertilization unit in Athens. PATIENT(S): A 40-year-old woman with a 10-year history of secondary infertility. INTERVENTION(S): Hysteroscopic diagnosis and removal of the bony fragment. MAIN OUTCOME MEASURE(S): Elimination of secondary infertility caused by osseous metaplasia. RESULT(S): After treatment, the woman underwent an IVF program and a healthy neonate was born with cesarean section. CONCLUSION(S): Hysteroscopy remains the best practice for the diagnosis and removal of endometrial ossifications, causing secondary infertility.

Adult↗