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Biomedical subjects

H S Cooper

Publications and source records attributed to H S Cooper.

At least 19 recordsLinked to original sources
PubMed1999

Combination therapy of pentoxifylline and TNFalpha monoclonal antibody in dextran sulphate-induced mouse colitis.

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) has been suspected of playing an important role in the pathogenesis of inflammatory bowel diseases, and has become a target for the treatment of these diseases. Open-label, placebo controlled studies have shown that engineered CDP571 and chimeric anti-TNF antibody (cA2) provide a significant benefit in Crohn's disease. Since these antibodies have to be used repeatedly to maintain remission in inflammatory bowel disease, there is a concern that their use may compromise host defence and produce toxic side-effects. METHODS: We evaluated the combined use of mouse specific TNFalpha mab (25 microg/mouse, Endogen) and pentoxifylline (PF, 100 mg/kg/day, p.o., TNFalpha release inhibitor) in the DSS (3% dextran sulphate solution) model of mouse colitis. Colitis was induced by the feeding of 3% DSS for three cycles. The study groups were: Group I: single injection of rat anti-mouse IgG, Group II: single injection of TNFalpha mab, Group III: daily PF for three cycles, Group IV: single injection of TNFalpha mab + PF for three cycles, Group V: TNFalpha mab at the beginning of each cycle (three injections) and Group VI: TNFalpha mab (three injections) + daily PF for three cycles. Daily disease activity (DAI) was measured throughout the study. At the end of each cycle, colon tissue was processed for histology, myeloperoxidase (MPO) and plasma TNFalpha. RESULTS: Mice treated with a single injection of TNFalpha alone or TNFalpha mab + PF showed significantly lower DAI, inflammation scores and ulcer index compared with the IgG treated group. Mice treated with TNFalpha mab + PF had no ulcers. Multiple injections of TNFalpha mab or TNFalpha mab + PF showed greater inhibition in DAI and cytokines in the first two cycles. However, in the third cycle, multiple injections of TNFalpha mab showed adverse proinflammatory effects. CONCLUSION: The simultaneous administration of pentoxifylline and TNFalpha mab may enhance therapeutic outcomes in inflammatory bowel disease and reduce the side-effects associated with the repeated use of TNFalpha mab.

Animals↗
PubMed1999

Depletion of colonic detoxication enzyme activity in mice with dextran sulphate sodium-induced colitis.

BACKGROUND: The increased risk of colonic malignancies in individuals with ulcerative colitis has prompted a search for early biomarkers of disease progression. AIM: To characterize Phase II detoxication enzyme expression during acute and chronic colitis. The mouse model of dextran sulphate sodium (DSS)-induced colitis represents a relevant system with which to sequentially evaluate the spectrum of biochemical changes associated with colorectal cancer risk. METHODS: Acute and chronic colitis were induced in Swiss Webster mice by administering DSS in the drinking water (5%) for 1-4 cycles. Each cycle consisted of 7 days DSS and 14 days of water. The glutathione S-transferase (GST) activity, gamma-glutamylcysteine synthetase (gamma-GCS) activity and glutathione content of the colonic tissues were determined at various time points throughout the experiment. Alterations in GST isozyme expression were confirmed by Western and Northern blot. RESULTS: GST activity was reduced significantly in the colon by the end of Cycle 1 (84% of control values). Specific activities continued to decrease with subsequent cycles of DSS exposure. By the end of Cycle 4, glutathione levels and gamma-GCS activity had reached 29% and 56% of control, respectively. CONCLUSIONS: These data suggest that detoxication enzyme depletion is associated with both acute and chronic colitis and may be an important event in the progression of ulcerative colitis to colon cancer.

Animals↗
PubMed1998

Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer.

PURPOSE: To determine the acute toxicity, post-operative complications, pathologic response and extent of downstaging to high dose pre-operative radiation using a hyperfractionated radiation boost and concurrent chemotherapy in a prospective Phase I trial. MATERIALS & METHODS: To be eligible for this study, patients had to have adenocarcinoma of the rectum less than 12 cm from the anal verge with either Stage T4 or T3 but greater than 4 cm or greater than 40% of the bowel circumference. All patients received 45 Gy pelvic radiation (1.8 Gy per fraction). Subsequent radiation was given to the region of the gross tumor with a 2 cm margin. This "boost" treatment was given at 1.2 Gy twice daily to a total dose of 54.6 Gy for Level I, 57 Gy for Level II, and 61.8 Gy for Level III. 5-FU was given at 1g/m2 over 24 hours for a four day infusion during the first and sixth weeks of radiation, with the second course concurrent with the hyperfractionated radiation. Surgical resection was carried out 4-6 weeks following completion of chemoradiation (in curative cases) and additional adjuvant chemotherapy consisting of 5-FU and Leucovorin was given for an additional 4 monthly cycles Days 1 through 5 beginning four weeks post surgery. RESULTS: Twenty-seven patients, age 40-82 (median 61), completed the initial course of chemoradiation and are included in the analysis of toxicity. The median follow-up is 27 months (range 8-68). Eleven patients were treated to a dose of 54.6 Gy, nine patients to 57 Gy, and seven patients to 61.8 Gy. Twenty-one patients had T3 tumors, and six patients T4 tumors. Grade III acute toxicity from chemoradiation included proctitis (5 patients), dermatitis (9), diarrhea (five), leukopenia (1), cardiac (1). Grade IV toxicities included one patient with diarrhea (on dose Level I) and one patient (on dose Level III) with cardiac toxicity (unrelated to radiation). Surgical resection consisted of abdominal perineal resection in 16 and low anterior resection in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I & II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p=.04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) > or = 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p=0.017). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p= 0.04). Older age (> or =61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting.

Adenocarcinoma↗
PubMed1998

Class III beta-tubulin isotype (beta III) in the adrenal medulla: II. Localization in primary human pheochromocytomas.

BACKGROUND: The Class III beta-tubulin isotype (beta III) is expressed specifically in central and peripheral nervous system neurons at various stages of neuronal differentiation. We have shown previously that beta III is expressed in a differentiation-dependent manner in human neuroblastomas arising in the adrenal medulla and sympathetic chains (Katsetos et al., Clin Neuropathol 13:241-255, 1994). The neuronal distribution of beta III in the developing and mature human adrenal medullae is detailed in the companion article (Katsetos et al., 1998A). METHODS: We have compared the localization of the neuronal beta III to S-100 protein, a sustentacular cell marker, in 14 formalin-fixed, paraffin-embedded primary human pheochromocytomas of the adrenal medulla and 14 adrenocortical tumors (adenomas and carcinomas). RESULTS: In pheochromocytomas, beta III staining was present in all tumors, but the number of stained cells varied in the two neural neoplastic phenotypes. Although the majority of chromaffin-like cells were beta III-positive, there was a lack of beta III in one-third of the tumor cells. Compared to chromaffin-like phenotypes, neuronal (ganglion-like cells) were invariably beta III-positive. Stromal sustentacular cells, stromal fibroblasts, and tumor blood vessels were beta III-negative. Sustentacular cells in pheochromocytomas were S-100 protein-positive, but beta III-negative. Primary adrenocortical tumors were beta III-negative with the exception of rare beta III-positive cells demonstrated in one case. CONCLUSIONS: The distribution of beta III in human pheochromocytomas of the adrenal gland is differentiation-dependent, closely recapitulating chromaffin cell and neuronal phenotypes of the normal adrenal medulla. Our findings indicate that beta III may be used as one of the adjuvant neural markers in the differential diagnosis of adrenal tumors, i.e., pheochromocytoma versus adrenocortical carcinoma. The occurrence of rare beta III-positive cells in cortical carcinomas is exceptional and probably represents the acquisition of a divergent neuroendocrine phenotype. The significance of the latter is unclear, although it may constitute a marker for malignancy.

Adrenal Cortex Neoplasms↗
PubMed1998

Preoperative chemotherapy of chemoradiotherapy for the treatment of adenocarcinoma of the pancreas and ampulla of Vater.

Much has been written about preoperative strategies in the treatment of pancreatic adenocarcinoma, yet there has been very little comment concerning other periampullary malignancies. This review discusses current issues relevant to the further development of preoperative adjuvant treatment of pancreatic adenocarcinoma. A small series of patients with ampullary adenocarcinomas treated with preoperative adjuvant chemoradiotherapy is also described.

Adenocarcinoma↗
PubMed1998

Cellular distribution of retinoic acid receptor-alpha protein in serous adenocarcinomas of ovarian, tubal, and peritoneal origin: comparison with estrogen receptor status.

Retinoids are effective growth modulators of human ovarian carcinoma cell lines. Their effects are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are transcriptional factors and members of the steroid/thyroid receptor superfamily. To our knowledge, until now, the cellular distribution of RAR proteins in human ovarian tumor specimens is unknown. This study provides new data on the differential cellular localization of RAR alpha protein in 16 serous adenocarcinomas originating from the ovaries, fallopian tubes, and the peritoneum. Using an affinity-purified antiserum specific for RAR alpha and a monoclonal antibody recognizing the full-length estrogen receptor molecule (clone 6F11), we performed immunohistochemistry on frozen tissue sections and examined the relationship between RAR alpha and estrogen receptor protein expression by comparing the percentage of immunostained tumor cells for either receptor. Our findings indicate a strong linear relationship between the percentages of RAR alpha- and estrogen receptor-labeled tumor cells as determined by linear regression analysis (P < 0.005, r = 0.825). A modest inverse relationship was found between the percentage of RAR alpha-positive tumor cells and histological grade, attesting to a differentiation-dependent trend (P < 0.04). No significant relationship was found between RAR alpha-labeled cells and clinical stage (P = 0.139), site of tumor origin (ovaries versus fallopian tubes versus peritoneum) (P = 0.170), and primary versus metastatic lesion (P = 0.561). Thus, serous adenocarcinomas are capable of expressing RAR alpha and estrogen receptor despite high histological grade and advanced stage of neoplastic disease. Compared with the heterogeneous localization of RAR alpha in cancer cells, there was widespread RAR alpha immunoreactivity in tumor-infiltrating lymphocytes, vascular endothelial cells, and stromal fibroblasts, underscoring the value of immunohistochemistry in the accurate determination of RAR/(RXR) content in tumor specimens.

Adenocarcinoma↗
PubMed1998

CD44V6 expression in human colorectal carcinoma.

CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix interactions. This transmembrane glycoprotein exists in either standard or variant forms, originated by alternative splicing. One of the isoforms (CD44V6) has been shown, in some systems, to modify the metastatic potential of tumor cells. To investigate the role of this biomarker as possible prognostic antigen in colorectal cancer, we immunohistochemically analyzed the distribution of CD44V6 expression on formalin-fixed, paraffin-embedded tissues from resected colorectal cancers of 34 patients. The monoclonal antibody VFF7 against the amino acid sequence encoded by exon CD44V6 was applied using the avidin-biotin-peroxidase method. For each resected specimen, normal (N), adenomatous (AD), and carcinomatous (CA) colonic mucosa were tested. In 68% of the resected cases, these areas were present in the same slide, and in 76% of cases, nodal or liver metastases (MT) were available for evaluation. Adenomatous polyp biopsy specimens of 10 carcinoma-free patients were also tested. In selected cases, CD44V6 expression was also determined using the Western blot immunoprecipitation technique. CD44V6 immunoreactivity was detected in 100% of the ADs, and in 91% of CAs, but was mostly weak in only 38% of MTs (n=26). In 49% (n=35) of ADs, 11% (n=34) of CAs, and 4% of MTs (n=26), the stain was moderate to strong. CD44V6 immunoreactivity was predominantly membranous in ADs and cytoplasmic in MTs. In the CAs, both staining patterns were noted. Interestingly, the normal mucosa had a weak subnuclear localization of the stain. In the cases evaluated by Western blotting immunoprecipitation analysis, the level of CD44V6 protein expression was similar to that obtained by immunohistochemistry. No correlation was found with tumor type, stage, or patient survival. The predominant CD44V6 expression in ADs and CAs, but not in MTs, suggests that, in many cases, the expression of this adhesion molecule may be lost during the acquisition of migratory function by the tumor cells.

Adenocarcinoma↗
PubMed1996

Primary combined malignant melanoma and ductal carcinoma of the breast. A report of two cases.

BACKGROUND: Tumors consisting of a combination of malignant melanoma and carcinoma are very rare. The authors report two such cases occurring as primary breast tumors. METHODS: The breast tumors were analyzed by histologic, immunohistochemical, and ultrastructural techniques. RESULTS: Histologically, the tumors were composed of a closely related admixture of ductal adenocarcinoma and malignant melanoma with abundant melanin pigment. Ductal carcinoma in situ was identified in both cases, confirming their origin in the breast. In both tumors, double-labeling immunohistochemistry showed that the epithelial component was immunoreactive for cytokeratin, the melanoma component was immunoreactive for HMB45, and both components were immunoreactive for S-100 protein. Immunostains for estrogen and progesterone receptors were negative in both tumors. Electron microscopy demonstrated glandular lumens and junctional complexes in the epithelial component and melanosomes and premelanosomes in the melanoma component. In one of the cases, rare tumor cells contained both premelanosomes and desmosomes. CONCLUSIONS: Combined malignant melanoma and carcinoma is a rare tumor. Only a handful of cases have been reported. The authors report two such cases occurring as primary tumors of the breast. The histology of the tumors revealed a closely related admixture of pigmented malignant melanoma and ductal carcinoma. Double-labeling immunohistochemistry showed that cytokeratin and HMB45 were expressed in the tumors, but not within the same cells. The authors propose describing this type of lesion as a single tumor of breast origin with bidirectional differentiation.

Adult↗
PubMed1995

Elevated expression of H type GDP-L-fucose:beta-D-galactoside alpha-2-L-fucosyltransferase is associated with human colon adenocarcinoma progression.

GDP-L-fucose:beta-D-galactoside alpha-2-L-fucosyltransferase (EC 2.4.1.69) is a key enzyme in the biosynthesis of fucosylated type 1 and 2 lactoseries structures, such as Lewis b and the H type 2 and Lewis Y, respectively, that are accumulated in colon adenocarcinoma. Analysis of the mRNA transcript level for the human H gene-encoded beta-D-galactoside alpha-2-L-fucosyltransferase revealed 40- and 340-fold increases in the mRNA levels in all adenocarcinomas and tumor cell lines, respectively, compared to normal colon mucosa where a low level of mRNA transcript was detected. A variable increase in mRNA transcript levels was observed in 50% of adenomatous polyps. Nucleotide sequence analysis of the protein coding region of the cDNAs derived from normal colon, adenoma, and colon adenocarcinoma revealed 100% homology, suggesting that there are no tumor-associated allelic variations within the H beta-D-galactoside alpha-2-L-fucosyltransferase cDNA. These results suggest that beta-D-galactoside alpha-2-L-fucosyltransferase expression highly correlates with malignant progression of colon adenocarcinoma.

Adenocarcinoma↗
PubMed1995

Endoscopically removed malignant colorectal polyps: clinicopathologic correlations.

BACKGROUND/AIMS: Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS: Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS: Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS: This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Colonic Polyps↗
PubMed1995

Mycosis fungoides palmaris et plantaris.

BACKGROUND: Mycosis fungoides primarily localized to the palms and soles is rare and has been previously reported as cutaneous lymphoma in four patients or as Woringer-Kolopp disease in eight patients. OBSERVATIONS: Four patients were initially diagnosed and treated unsuccessfully for various palmoplantar dermatitides until histopathologic findings revealed mycosis fungoides. Each case exhibited a clonal rearrangement of T-cell receptor gamma genes and immunohistochemical studies consonant with mycosis fungoides. All patients had limited skin involvement without evidence of extracutaneous involvement. CONCLUSIONS: Mycosis fungoides palmaris et plantaris is an uncommon expression of mycosis fungoides that manifests primarily on the palms and soles and clinically may mimic various inflammatory palmoplantar dermatoses. A biopsy is recommended in the evaluation of recalcitrant palmoplantar dermatoses.

Diagnosis, Differential↗
PubMed1994

Novel immunohistochemical localization of 28,000 molecular-weight (Mr) calcium binding protein (calbindin-D28k) in enterochromaffin cells of the human appendix and neuroendocrine tumors (carcinoids and small-cell carcinomas) of the midgut and foregut.

Calbindin-D28k is a highly conserved 28,000 (dalton) molecular-weight (Mr) calcium binding protein with broad tissue distribution, yet cell-type-specific expression predominantly in subpopulations of central and peripheral nervous system neurons, distal tubular cells of the kidney, and enteric neuroendocrine cells. A polyclonal antiserum against rat renal calbindin-D28k and a monoclonal antibody to calbindin-D28k purified from chicken intestine (clone CL-300) were used for immunohistochemical evaluation of formalin-fixed, paraffin-embedded tissues from multiple areas of the human small and large intestines and 93 primary neoplasms of the gastrointestinal tract (foregut, midgut, and hindgut derivatives) and the lung (foregut derivative). Calbindin-D28k immunostaining was obtained in a minority of enterochromaffin (neuroendocrine) cells, predominantly of the appendix and small intestine, as well as in autonomic neurons of the neural plexuses. Focal cytoplasmic Golgi-type staining was obtained with monoclonal antibody CL-300 in the appendiceal surface epithelium and dendritic macrophages confined to the appendiceal lymphoid follicles. Epithelial progenitor cells in enteric crypts and absorptive, goblet, and Paneth cells were calbindin-D28k negative, while no immunoreactivity was demonstrated in the mucosae of the colon and rectum. Calbindin-D28k staining was consistently detected in subpopulations of neuroendocrine phenotypes in midgut (appendiceal/ileal) and foregut (bronchial) carcinoids and small-cell carcinomas, but was absent in adenocarcinomas, squamous cell carcinomas, leiomyomas/leiomyosarcomas, schwannomas, and lymphomas. Our observations suggest that calbindin-D28k is a novel adjuvant neuroendocrine marker that is potentially useful in diagnostic tumor immunohistochemistry.

Adult↗
PubMed1993

Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin.

The use of oral and intravenous cyclosporin represents a significant advance in the therapy of refractory inflammatory bowel diseases (IBD). However, oral administration of cyclosporin is fraught with improper delivery of cyclosporin to the colon for its topical action. Because of unpredictable metabolism by cytochrome P-450 IIIA, the targeted blood level for systemic effect is not reached at low doses. Furthermore, the doses that have been used for therapy of IBD have been shown to induce several adverse side effects. Thus, an alternate method of delivering cyclosporin to the colon is desirable. In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000-40,000 mol wt) for five or seven days, respectively. Therapy was advocated prophylactically, prophylaxis plus therapy and therapeutically during the acute and chronic phase of the disease and therapeutically during the chronic phase of the disease. Intracolonic cyclosporin given prophylactically showed adverse effects by increasing the damage to the colonic mucosa. However, intracolonic cyclosporin given therapeutically in 2.5, 5, and 10 mg/kg after the induction of colitis resulted in dramatic responses in terms of reducing the disease activity and histologic scores, corroborated by complete histological resolution compared to oral cyclosporin given at identical doses. Intracolonic cyclosporin (5 mg/kg) was also very effective in reducing the chronic inflammation. The results of this study highlight the application of this animal model for therapeutic research. Furthermore, cyclosporin administered as an enema provides a new stratagem for the therapy of IBD because of its rapid onset of action at very low doses without the risk inherent in oral or systemic administration.

Acute Disease↗
PubMed1993

Clinicopathologic study of dextran sulfate sodium experimental murine colitis.

BACKGROUND: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. EXPERIMENTAL DESIGN: Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms. RESULTS: Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease. CONCLUSIONS: The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease.

Animals↗
PubMed1992

Adenomyoepithelioma of the breast. A spectrum of biologic behavior.

Adenomyoepitheliomas of the breast have been considered to have limited metastatic potential; axillary node metastasis has been reported, but there has been no report of distant metastasis. We report six cases, including two malignant adenomyoepitheliomas, one of which metastasized to the lung and brain. Patient age ranged from 26 to 63 years (mean 46). Primary tumors were solitary and measured 0.9-3.5 cm (mean 1.7). Five of six tumors presented as palpable masses. Two patients treated by local resection have no evidence of disease at 5 and 18 months' follow-up. Two patients treated by local resection had recurrences, one at 48 the other at 60 months. The fifth patient had a spindle-cell type adenomyoepithelioma diagnosed as malignant because of high mitotic rate and cytologic atypicality of the myoepithelial component. This patient was treated by mastectomy and has no evidence of disease at 18 months. The sixth patient, initially treated by local excision, had six local recurrences over 52 months treated by reexcisions, mastectomies, and radiation. A lung metastasis was resected at 54 months and brain metastases were identified at 60 months with death occurring at 64 months. Both malignant adenomyoepitheliomas had high mitotic rates [11-14/10 high-power fields (HPF)] diffusely throughout the tumors and foci of cytologically malignant cells. The malignant adenomyoepithelioma that metastasized had an infiltrative growth pattern that increased with successive local recurrences. The four other tumors had only isolated areas of mitotic activity (maximum 1-9/10 HPF) and minimal cytologic atypia. Immunohistochemistry performed on five of six cases confirmed dual epithelial/myoepithelial cell populations in all tumors examined, including the metastasis. Electron microscopic examination of the malignant adenomyoepithelioma that metastasized also confirmed dual epithelial/myoepithelial cell populations in a local recurrence and the lung metastasis. We conclude that there is a spectrum of behavior for breast adenomyoepitheliomas with potential for local recurrence and, rarely, distant metastasis.

Adult↗
PubMed1991

Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.

In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes. The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell. Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors. These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt. Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments. Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell. The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway.

ABO Blood-Group System↗