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Biomedical subjects

A N Cheung

Publications and source records attributed to A N Cheung.

At least 37 records · Page 2Linked to original sources

Mitomycin chemotherapeutic pleurodesis to palliate malignant pleural effusions secondary to gynecological cancer.

BACKGROUND: To assess the efficacy of mitomycin pleurodesis in women with end stage malignant effusion. METHODS: Retrospective analysis. RESULTS: Of the 13 patients treated six had ovarian, six had endometrial and one had cervical adenocarcinoma. The median time of onset of effusion from diagnosis of primary disease was 12 months (range 1-75). Ten patients were evaluable for response. The median age of the patients was 59 years (range 42 to 74). Ten (77%) of them had repeated thoracocentesis prior to mitomycin pleurodesis. The median duration and volume of drainage was 4 days (range 2-11) and 3.1 liters (range 1.2-10.2) respectively. One of two patients developed a pneumothorax and required the insertion of an additional chest drain. Overall, seven patients (70%) responded - one completely (CR) and six partially (PR), while three did not respond. Four of five patients with ovarian cancer had a partial response, two of four patients with endometrial cancer (one CR and one PR) responded. The only patient with cervical cancer had a partial response. Nine patients (69%) had enough symptomatic improvement to be discharged home. The drug cost of bleomycin 60 units (US$191), another commonly used agent, was more than twice as expensive as mitomycin 30 mg (US$84). CONCLUSIONS: Mitomycin pleurodesis can palliate 70% of patients for at least 1 month. It offers cheap and effective palliation. There is a suggestion that patients' quality of life is improved.

Adult↗

Apoptosis in gestational trophoblastic disease is correlated with clinical outcome and Bcl-2 expression but not Bax expression.

Apoptosis has been found to play a crucial role in the pathogenesis and prognosis of many human diseases. The pathogenesis of gestational trophoblastic disease (GTD), which encompasses hydatidiform moles (HMs) and choriocarcinomas (CCAs), is not fully understood. Prognostic indicators of HM have also been scanty. In this study, we investigated apoptotic activity and the expression of two apoptosis regulatory genes, Bcl-2 and Bax, in an attempt to determine the role of apoptosis in GTD. Formalin-fixed paraffin-embedded tissue of 33 normal placentas, 14 spontaneous abortions, 14 partial moles, 34 complete moles, and eight CCAs were examined. Apoptotic activity was assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. Quantitative assessment of apoptotic index (AI) was calculated as a percentage of TUNEL-positive nuclei. Expression of Bcl-2 and Bax were assessed immunohistochemically. Extensive apoptosis was located in syncytiotrophoblasts, cytotrophoblasts, and villous stromal cells in all HM cases. Apoptosis was detected at a much lower level in spontaneous abortions and normal placentas. Moreover, in normal placentas, TUNEL positive nuclei were exclusively found in syncytiotrophoblasts. AIs were significantly different among various categories of trophoblastic lesions (P < .001) in an ascending order: normal placentas less than spontaneous abortions less than CCAs less than HMs. Furthermore, AIs of those cases that spontaneously regressed was statistically higher than those that developed persistent trophoblastic disease requiring chemotherapy. AIs of trophoblastic lesions in general inversely correlated with Bcl-2 expression (P < .001), but no significant correlation was found between AI and Bax expression (P > .5). We conclude that AI may be a useful prognostic marker for clinical progress of HMs. Bcl-2 expression is probably regulating apoptosis in normal placentas and GTD, whereas Bax expression is not. The difference in AI and Bcl-2 expression between non-molar placentas and HMs offers a potential adjunctive diagnostic tool to distinguish the two entities.

Apoptosis↗

Pseudomyxoma peritonei--a heterogenous disease.

OBJECTIVE: To evaluate the origin of pseudomyxoma peritonei (PMP) in Chinese women. METHODS: The clinicopathologic features of 15 cases of PMP were reviewed. Immunostaining using antibodies for CK7 and CK20 was performed in the ovarian, appendiceal and peritoneal lesions of these cases. RESULTS: Appendiceal pathology was documented in five cases, including four mucinous cystadenoma and one simple mucocele. Eight ovarian tumors were found, including seven mucinous cystadenocarcinomas of low malignant potential and one mucinous cystadenoma. Synchronous ovarian and appendiceal lesions were discovered in three cases. One patient had adenocarcinoma of the pancreas. The origin of mucin production was not known in four cases with metastatic adenocarcinoma found in two of them. Immunoreactivity for CK20 was demonstrated in the tissues derived from the peritoneum, ovary, appendix and pancreas while only 23% (3 out of 13 women) of the peritoneal lesions and 33% (2 out of 6 women) of the ovarian tumors were immunoreactive for CK7. CONCLUSIONS: PMP is a heterogeneous lesion, which may develop from mucinous metaplasia of the peritoneum or from appendiceal, or ovarian lesions. Careful examination of the ovary and appendix with performance of appendectomy is advised in every case of PMP. Immunohistochemical examination of the peritoneal, ovarian or appendiceal lesions using antibodies, in particular that for CK7 would help in defining the origin of mucin production.

Adult↗

Detection of trisomy 3 in primary gastric B-cell lymphoma by using chromosome in situ hybridization on paraffin sections.

Recent studies in Western populations have shown that trisomy 3 is the most frequent chromosomal abnormality in primary gastric lymphoma (PGL). To study the incidence of trisomy 3 and its implications for the pathogenesis of PGL in Hong Kong, we have applied the technique of chromosome in situ hybridization in 13 cases of PGL by using archival paraffin-embedded tissue sections. Five cases of chronic gastritis were used as controls. Trisomy 3 was found in 9 (69%) of 13 cases, including cases of low-grade lymphoma and high-grade lymphoma with or without a low-grade component. Our findings are similar to the incidence of trisomy 3 reported in the Western literature. The persistent finding of trisomy 3 in various histologic grades of PGL suggests that it may be useful as a clonal marker in this group of neoplasms. Various molecular events involving chromosome 3 may be related to the pathogenesis of this group of lymphomas.

Chromosomes, Human, Pair 16↗

Ovarian mature cystic teratoma with malignant transformation. An interphase cytogenetic study.

The chromosomal composition of cancers arising in ovarian mature cystic teratoma (MCT) was analyzed using chromosome in situ hybridization (CISH) performed on paraffin-embedded material from 10 squamous cell carcinomas, 1 adenocarcinoma, 1 thyroid papillary carcinoma, and 1 strumal carcinoid. Cervical tissue from seven of these patients was used as a control. In the cancers, a relative gain of chromosome 16 (in 7 cases), chromosome 12 (in 9), chromosome 11 (in 10), and chromosome X (in 8) was detected. Trisomy 12 was diagnosed in eight cases. No chromosomal aberrations were detected in the strumal carcinoid. In the benign areas of the MCTs, only one case showed a gain of chromosome 11, although, in another case, there was a gain of chromosome X. Malignant transformation of MCTs often occurs in association with complex chromosome aberrations that may play a role in the development of such carcinomas.

Adenocarcinoma↗

p21WAF1/CIP1 expression in gestational trophoblastic disease: correlation with clinicopathological parameters, and Ki67 and p53 gene expression.

BACKGROUND: The p21WAF1/CIP1 gene mediates growth arrest by inhibiting G1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53. AIM: To analyse the role of p21WAF1/CIP1 in gestational trophoblastic disease. METHODS: The immunohistochemical expression of p21WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress. RESULTS: p21WAF1/CIP1 immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21WAF1/CIP1 protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21WAF1/CIP1 expression compared with normal placentas and partial hydatidiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21WAF1/CIP1 expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21WAF1/CIP1 expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not. CONCLUSIONS: This study suggests that p21WAF1/CIP1 expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21WAF1/CIP1. p21WAF1/CIP1 expression is not an accurate prognostic indicator of gestational trophoblastic disease.

Biomarkers, Tumor↗

Tumour markers and their prognostic value in adenocarcinoma of the cervix.

Ninety-one patients with adenocarcinoma of the cervix had 4 tumour markers (TMs) assayed before treatment. Serum squamous cell carcinoma antigen (SCC) (n = 91) was raised in 25%; tissue polypeptide antigen (TPA) (n = 78) was raised in 35%; carcinoembryonic antigen (CEA) (n = 34) was raised in 26% and CA 125 (n = 64) was raised in 27% of these patients. In 47 of these 91 patients (52%), 1 or more of the markers were raised. The percentage of patients with raised TM increased with advancing stage. Univariate survival analysis showed that age, stage, raised TPA, raised CA 125, and raised TMs (any one or more) were of prognostic significance. When multivariate analysis was done and each TM was individually analysed, only age, stage and raised CA 125 were of prognostic significance. Rising SCC or TPA or CA 125 levels in serial estimations correlated well with the occurrence of recurrence. Thus, pretreatment estimation of SCC, TPA and CA 125 can be used to identify the patients who can subsequently be monitored by serial TM estimation.

Adenocarcinoma↗

Post-transplantation lymphoproliferative disorder of donor origin in a sex-mismatched renal allograft as proven by chromosome in situ hybridization.

We report a case of post-transplantation B-cell lymphoproliferative disorder (PTLPD) associated with Epstein-Barr virus (EBV) that developed in a renal allograft 5 months after transplantation. The lesion had a histologic appearance of diffuse large B-cell lymphoma with monoclonality demonstrated by in situ hybridization (ISH) for kappa and lambda mRNA. Both the male donor and the female recipient were EBV seropositive. The lymphoid cells in this lesion was proven to be of donor origin by ISH for the human Y chromosome on the paraffin-embedded sections of the allograft. The recipient of the other kidney from the same donor did not have evidence of lymphoma, and the patient was also free from disease 2 years after surgical removal of the lymphoma This case is an unusual PTLPD of donor origin; the majority of such lesions in solid organ transplantations are of recipient origin. Our findings demonstrate that the origin of PTLPD can be documented in selected cases using ISH with probes to the Y chromosome.

Adult↗

Is immunostaining with HAM56 antibody useful in identifying ovarian origin of metastatic adenocarcinomas?

HAM56 (human alveolar macrophage) is a monoclonal antibody that reacts with macrophages and endothelial cells. There has been controversy as to its usefulness in differentiating adenocarcinomas of ovarian or gastrointestinal origin. The aim of this study is to test the specificity of HAM56 in identifying the origin of metastatic adenocarcinomas. Ninety-two adenocarcinomas of known primary site, metastatic to omentum or lymph nodes were used. Immunostaining for HAM56 was performed on formalin-fixed, paraffin-embedded tissue after antigen retrieval with microwave pretreatment. Positive immunostaining was shown as membrane or cytoplasmic staining with luminal accentuation. Nonspecific staining in necrotic debris or mucin was excluded. Immunoreactivity for HAM56 was found in 37 metastatic adenocarcinomas; 22 of 31 cases (71%) of ovarian origin, 7 of 33 (21%) of colonic origin, 4 of 16 (25%) of gastric origin, 3 of 6 (50%) of biliary origin; and 1 of uterine origin (100%). Negative staining was found in adenocarcinomas from the pancreas (n = 2), cervix (n = 2), and fallopian tube (n = 1). These findings suggest that HAM56 reacts with adenocarcinomas arising from several origins though with a higher frequency in ovarian tumors. It is thus not specific for ovarian carcinomas and is, therefore, not a useful tool to help distinguish adenocarcinomas of unknown origin.

Adenocarcinoma↗

Mixed low grade and high grade endometrial stromal sarcoma of uterus: differences on immunohistochemistry and chromosome in situ hybridisation.

A case of a 64 year old woman with a tumour of the uterus is reported. The patient presented with postmenopausal bleeding and subsequently underwent total hysterectomy and bilateral salpingo-oophorectomy. Sections of the tumour showed a low grade endometrial stromal sarcoma coexisting with areas consistent with high grade sarcoma. The sarcoma cells, in both the low and high grade areas, were positive for vimentin and negative for desmin and cytokeratin on immunohistochemistry. While the sarcoma cells in the low grade region showed immunoreactivity for oestrogen and progestogen receptors, those in the high grade region did not. Using chromosome in situ hybridisation, the low grade portion of the sarcoma was diploid for chromosomes X, 11, 12, and 17, whereas the more anaplastic areas were aneuploid for these chromosomes. This case may represent an example of high grade endometrial stromal sarcoma arising by dedifferentiation from a low grade stromal sarcoma. Adequate sampling is important in identifying such anaplastic changes as the origin of the tumour will affect patient management.

Chromosome Aberrations↗

Oncogenes and other growth factors in gynaecological neoplasms.

Major findings from recent studies of oncogenes and growth factors in gynaecological neoplasms are reviewed in this article, with special emphasis on carcinomas of the ovary and endometrium. The significance of oncogenes and growth factors in carcinogenesis and tumour progression is discussed.

Biomarkers, Tumor↗

Interphase cytogenetic study of endometrial stromal sarcoma by chromosome in situ hybridization.

Endometrial stromal neoplasms include a heterogenous group of tumors with different clinical behavior and response to treatment. Cytogenetic study of such tumors has been scanty. The aim of this study was to analyze and compare the chromosome composition in low-grade and high-grade endometrial stromal sarcoma using the technique of chromosome in situ hybridization. Eight cases of low-grade stromal sarcoma and three cases of high-grade stromal sarcoma were studied. Biotinylated DNA probes specific for the regions of chromosomes X, 11, 12, and 17 were used on formalin-fixed paraffin embedded material from these tumors. The in situ hybridization signals were visualized by immunoperoxidase technique. Four of the eight low-grade stromal sarcomas retained normal disomy of the chromosomes studied. The other four low-grade sarcomas showed a gain of from one to three chromosomes, whereas all of the three high-grade sarcomas showed polysomies in all of the four chromosomes being studied. No loss of chromosomes was detected. One case of high-grade sarcoma contained coexisting areas of low-grade sarcoma. Although aneusomy was found in the high-grade portion, disomy was noted in the low-grade areas. In the stromal sarcomas studied, there was no definite correlation between the presence of chromosome polysomies and the clinical progress of the tumors. This is the first interphase cytogenetic study of uterine stromal sarcoma, and the results support the concept that complex numerical chromosome abnormalities evolve during anaplastic transformation of endometrial stromal sarcoma.

Adult↗

Prognostic significance of serum tumour markers in carcinoma of the cervix.

PURPOSE: The purpose was to evaluate the prognostic significance of serum tumour markers and other potential prognostic factors in cervical cancer. MATERIALS AND METHODS: Five hundred and thirty-one patients with cervical cancer were studied. The pre-treatment levels of SCC (squamous cell carcinoma antigen), TPA (tissue polypeptide antigen), CEA (carcinoembryonic antigen), CA125 and hCG (human chorionic gonadotrophin) were assayed in these patients. Possible association between raised tumour markers and potential prognostic factors and their prognostic significance were sought by univariate and multivariate Cox analysis. RESULTS: SCC was raised in 65% of squamous cell carcinoma of the cervix and TPA was raised in 50%. Other markers were raised in less than 25%. No tumour markers were raised more than 30% in adenocarcinoma of the cervix. Raised SCC and TPA were related to advancing age, stage and grade of differentiation. Univariate analysis showed that age, stage, grade, raised SCC and TPA were significant prognostic factors on survival. Multivariate Cox analysis showed that stage was the most significant factor. CONCLUSION: Stage, age, grade of differentiation, raised pre-treatment levels of SCC and TPA were significant prognostic factors in cervical cancer using univariate analysis. However, only stage remains the most important independent prognostic factor in multivariate analysis. The prognostic value of these other factors in early stage disease needs further exploration.

Adenocarcinoma↗

The mRNAs for the three chains of human collagen type XI are widely distributed but not necessarily co-expressed: implications for homotrimeric, heterotrimeric and heterotypic collagen molecules.

In cartilage collagen type XI exists as heterotrimeric molecules composed of alpha 1(XI), alpha 2(XI) and alpha 3(XI) subunits. Messenger RNAs for some of the alpha chains of collagen type XI have also been found in non-chondrogenic tissues but the chain composition of the molecule in these sites is not known. Some non-chondrogenic tissues also contain heterotrimers containing collagen alpha 2(V) and alpha 1(XI) chains. We have explored the possibility that collagen type XI could exist in differing trimeric forms in non-chondrogenic tissues and aimed to predict the subunit composition of this collagen in those tissues. The distribution and relative levels of expression of collagen alpha 1(XI), alpha 2(XI) and alpha 3(XI)/alpha 1(II) mRNAs in different human fetal tissues were studied. Expression of mRNAs for all three genes of collagen type XI is not restricted to cartilage but is widespread. However, in some non-chondrogenic tissues, the mRNAs for all three alpha chains of collagen type XI were not co-expressed, but collagen alpha 1(XI) and alpha 2(XI) mRNAs were found either singly or without collagen alpha 3(XI) transcripts. Collagen type XI may therefore exist as homotrimers and/or heterotrimers composed of two collagen alpha(XI) chains in some tissues. The distribution of mRNAs for collagen alpha 2(V) and alpha 1(I) were also studied. Co-expression of collagen type XI, alpha 2(V) and alpha 1(I) mRNAs was found for many tissues. These findings have implications for the possibility of additional chain associations for collagen types XI and V in cross-type heterotrimers within heterotypic fibrils.

Cartilage↗

The expression of cathepsin D, oestrogen receptor and progestogen receptor in hydatidiform mole--an immunohistochemical study.

The expression of oestrogen and progestogen receptors, as well as Cathepsin D, an oestrogen-induced protease, in trophoblastic cells of 12 cases of complete hydatidiform mole, 12 cases of partial mole and nine cases of spontaneous abortions, were studied in an attempt to elucidate their possible roles in the pathogenesis of the diseases. The immunohistochemical studies were performed on formalin-fixed paraffin-embedded tissue using the ABC immunoperoxidase method. The intensity of staining and proportion of cells stained were assessed and compared in the three categories of lesions. Immunoreactivity for Cathepsin D was noted in both the syncytio- and cytotrophoblastic cells in all three lesions. Statistical analysis showed consistently stronger and more extensive staining for Cathepsin Din complete moles when compared with abortions. Staining for oestrogen and progestogen receptors was found to be weak in the tissues studied. The strong expression of Cathepsin D in trophoblastic cells of all three lesions, especially in complete mole, suggests that it might be important in the control of trophoblastic cell activities and involved in the pathogenesis of hydatidiform mole. The associated weak expression of sex hormone receptors also suggests that the expression of Cathepsin D in trophoblastic cells may be controlled by modes of regulation other than sex hormones.

Cathepsin D↗

Detection of heterozygous XY complete hydatidiform mole by chromosome in situ hybridization.

Complete hydatidiform mole has a substantial risk of developing persistent gestational trophoblastic disease (PTD). Whether heterozygous complete moles, arising from dispermy, have a higher risk of such progression than their homozygous counterparts is controversial. In this study, the frequency of heterozygous XY complete mole in 93 consecutive cases of histologically proven complete moles managed in Hong Kong was assessed by the technique of chromosome in situ hybridization (CISH) using DNA probes specific for the short arm of the Y chromosome. The incidence of Y-chromosome positive complete mole in the groups of patients with spontaneous remissions and the group with PTD with or without metastasis was also compared. The presence of Y chromosome was identified in 6 of the 93 cases (6.5%), and this incidence fell within the range reported in the world literature. Of these 93 patients, 5 patients defaulted follow-up, while 10 patients developed PTD, with evidence of metastasis in 2 of them. The presence of Y chromosome was also assessed in another 15 patients with documented metastatic PTD. It was found that CISH signals for Y chromosome were identified in 5.1% (4/78) of complete moles with spontaneous remission and 8% (2/25) with PTD with or without metastasis (P > 0.05). Y chromosome was detected in 5.9% (1/17) of the complete moles that developed metastasis and in 5.8% (5/86) of the complete moles that either developed spontaneous remission or developed nonmetastatic PTD (P > 0.05). There is no correlation between the presence of Y chromosome and development of persistent gestational trophoblastic disease.

Female↗