[Epidermal growth factor receptor family and targeted anticancer therapy].
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Antibodies, Monoclonal↗
Biomedical subjects
Tong-Hua Liu
Publications and source records attributed to Tong-Hua Liu.
Chromosome 1q loss of heterozygosity frequently occurs in sporadic insulinomas and is associated with tumor malignancy.
The pathogenesis of sporadic insulinomas is not clear, and there are no reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor. It was reported that 1q LOH might contribute to pathogenesis in gastrinomas and was correlated with tumor progression. However, little data are available on 1q LOH in sporadic insulinomas. In our study, we determine whether 1q LOH occurs in sporadic insulinomas and is associated with tumor malignancy by performing 1q allelotyping with 17 markers in 40 tumors and pair normal DNA. Thirty-five (88%) insulinomas had 1q LOH. Of the 35 insulinomas with 1q LOH, 14 (40%) had 1q21.3-23.2 LOH over a 7.5 cM region (SRO-1), whereas LOH in 21 tumors (60%) occurred at 1q31.3 over an 11.4 cM area (SRO-2). Of 24 tumors without MEN1 LOH, 20 had either SRO-1 or SRO-2 LOH (83%), whereas in 16 tumors with MEN1 LOH, 9 were shown to have LOH at either SRO-1 or SRO-2 (56%) (p = 0.065). This result suggests that LOH at 2 SRO might be MEN1 gene independent and may contribute to the pathogenesis in a subset of insulinomas without MEN1 gene LOH. The presence of 1q21.3-23.2 LOH is significantly associated with malignancy of insulinomas (p = 0.014). The high frequency of LOH at 1q 21.3-23.2 and 1q31.3 suggests these 2 areas may harbor putative tumor suppressor genes that may play an important role in the tumorigenesis of a subset of insulinomas. LOH at 1q21.3-23.2, which was associated with tumor malignancy, could be one of the genetic markers for identifying malignancy in sporadic insulinomas.
Adolescent↗
Hepatosplenic gammadelta T-cell lymphoma.
AIM: To investigate the clinicopathologic characteristics, immunophenotype and TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese patients. METHODS: Eight Chinese patients with hepatosplenic gammadelta T-cell lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories were reviewed. We also carried out immunohistochemical staining for CD3, CD4, CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR gammadelta. Rearrangements of TCR gamma and delta chain genes were also studied. RESULTS: The spleens were enlarged and the cut surfaces were homogeneous and red-purple in color without identifiable gross lesions or enlarged hilar lymph nodes. Histologically, lymphoma cells infiltrated the cords of Billroth and often packed the sinuses. Liver biopsy showed lymphoma cell infiltrations in the sinusoids, and three cases showed involvements of the portal tracts. Immunohistochemically lymphoma cells were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal rearrangements of TCR gamma gene were demonstrated by PCR analysis in five out of the eight cases. TCR delta gene rearrangements were detected in six out of the eight cases, which demonstrated single bands on PAGE gel, and the amplification products in two cases were confirmed by sequencing. CONCLUSION: The clinicopathology of hepatosplenic gammadelta T-cell lymphoma in Chinese patients is similar to what was previously reported except that the splenomegaly is not so massive, and CD8 is positive.
Adult↗
[Expression of survivin gene in pancreatic carcinoma].
OBJECTIVE: To determine the expression status of survivin gene in pancreatic carcinoma. METHODS: Expression of survivin gene was evaluated by immunohistochemistry, Western Blot and RT-PCR in 59 cases of pancreatic carcinoma along with their corresponding adjacent benign tissues, 11 cases of chronic pancreatitis, and 7 pancreatic carcinoma cell lines. RESULTS: The positive expression rate of survivin in pancreatic carcinoma was 72.8% (43/59). There was no relationship between the expression of survivin and tumor stage and differentiation. No expression of survivin was detected in benign tissue adjacent to the tumors as well as in samples of chronic pancreatitis. All 7 pancreatic carcinoma cell lines showed a positive expression of survivin mRNA and protein. CONCLUSIONS: The expression of survivin appears to be tumor specific to some extent in our pancreatic carcinoma samples. Survivin may be an ideal target for therapy against pancreatic carcinoma.
Adenocarcinoma, Mucinous↗
[Opportunity and challenge of diagnostic pathology in China].
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Autopsy↗
[Evaluation of HER2 gene expression status in breast cancer by fluorescence in-situ hybridization].
OBJECTIVE: To deduce the protocol, scoring criteria and interpretive guidelines for assessment of HER2 gene expression status by fluorescence in-situ hybridization (FISH) and to compare the results with those obtained by immunohistochemistry. METHODS: The HercepTest kit from Dako Cytomation was employed for immunohistochemistry. FISH for HER2 gene expression status was performed using PathVysion DNA probe kit on the archival paraffin-embedded sections of breast cancer tissues from 28 Chinese female patients with immunohistochemical staining scores of (3 +), (2 +), (1 +) and 0. RESULTS: Ten of the 12 patients with score (3 +) by immunohistochemistry were positive for HER2 by FISH, with 2 cases being polysomy. Two other cases with FISH-negative were also shown to be polysomy. Seven of the 10 patients with score (2 +) by immunohistochemistry showed HER2 gene amplification, with 1 case being polysomy. Two of the remaining 3 cases, which were FISH-negative, were shown to be polysomy. All the patients with scores (1 +, number = 3 ) or 0 ( number = 3) by immunohistochemistry failed to show amplification. One case of polysomy was noted in either group. CONCLUSIONS: Immunohistochemistry is useful as an initial screening tool for HER2 expression status. Because of the obvious discrepancies between protein expression and gene amplification, patients with score (2 +) by immunohistochemistry should undergo FISH testing as well. FISH is also required in selected examples with score (3 +) immunohistochemical results, especially in those with false-positive immunohistochemistry due to chromosome 17 aneuploidy.
Breast Neoplasms↗
[Clinicopathologic study of 10 cases of osteomalacia or rickets-associated mesenchymal tumors].
OBJECTIVE: To study the clinicopathologic features of osteomalacia or rickets-associated mesenchymal tumors. METHODS: The clinical and pathologic findings of 10 cases of osteomalacia or rickets-associated mesenchymal tumors were evaluated. Hematoxylin and eosin stain, immunohistochemistry and histochemistry were performed on the archival paraffin sections. RESULTS: Amongst the 10 patients studied, 6 were males and 4 were females. Their age at the time of operation ranged from 28 to 69 years ( mean = 45.6 years). A history of long-standing bone pain, arthralgia, limitation in movement, hypophosphatemia and hyperphosphaturia was present in all cases. The duration of symptoms ranged from 2 to 27 years (mean = 9.6 years). The tumor size ranged from 1 to 7 cm (mean size = 3.52 cm). Microscopically, the tumors were composed of various mesenchymal cells, including spindled fibroblast-like cells, adipocytes, chondroid cells and mucinous cells. The background was rich in blood vessels. In 8 of the 10 cases, there was also dystrophic calcification in an unusual flocculent or "grungy" pattern. Peripheral woven bone shell formation was noted in 2 cases and non-urate crystal deposition in 2 cases. Mitotic figures were rare in 9 cases. In 1 of the 10 cases however, mitotic figures and bizarre cells were commonly encountered. On immunohistochemical study, the tumor cells were all positive for vimentin. There was focal positivity for smooth muscle actin and CD34 in 5 and 3 cases respectively. The staining for desmin, S-100 and AE1/AE3 was negative. Ki-67 proliferation index was less than 4% in 8 cases and 30% in 1 case. Alcian blue-positive mucinous matrix and mucinous degeneration around vessels were noted in 8 cases. CONCLUSIONS: Most of the osteomalacia or rickets-associated tumors are either benign or low-grade malignant mesenchymal tumors. They can be mistaken as other neoplasms due to the morphologic heterogeneity present. Thorough understanding of the associated clinical features and laboratory investigation results is helpful in arriving at the correct diagnosis.
Actins↗
[Frequent loss of heterozygosity at MEN-1 gene and chromosome 22q in insulinomas and its significance].
OBJECTIVE: To detecte whether loss of heterozygosity (LOH) at the MEN-1 locus as well as 22q occurs in sporadic insulinoma and if LOH can be used as a genetic marker to differentiate malignant and benign insulinomas. METHODS: MEN-1 gene and 22q allelotyping were performed by PCR with microsatallite markers in DNA from microdissected normal and tumor tissues from archived or frozen insulinomas (8 malignant and 32 benign, from 38 patients). The significance was calculated using t test and Cochran-Mantel-Haenszel Statistics, P < 0.05 was considered significant. RESULTS: Sixteen of the 40 insulinomas (40.0%) had MEN-1 LOH and 22q LOH was shown in 30 of the 40 tumors (75.0%). Eleven of the 30 tumors (37.0%) with 22q LOH had 22q12 LOH over a 3 cm region, whereas LOH in 14 tumors (47.0%) occurred at 22q13.3. Eight tumors with D22S 280 locus (22q12) LOH were shown without MEN-1 LOH while 14 of the 30 tumors without D22S280 LOH had MEN-1 LOH (0% vs 47%, P = 0.016). Six of the 14 tumors (43.0%) with 22q13.3 LOH were malignant, whereas 2 of 26 tumors without 22q13.3 LOH (8.0%) are malignant (P = 0.0088). CONCLUSION: MEN-1 gene LOH may contribute to a proportion of insulinomas, and 22q LOH occurs frequently in insulinomas. D22S 280 (22q12) LOH may independently contribute to the tumorogenesis of sporadic insulinoams, whereas detecting 22q13.3 LOH in insulinomas can be a potential genetic marker to distinguish malignancy from benign tumors.
Biomarkers, Tumor↗
[The advances of histopathology and molecular pathology of endocrine tumors].
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Biomarkers, Tumor↗
[Distinction between benign and malignant pheochromocytomas].
OBJECTIVES: To investigate the differences in morphology, immunohistochemistry, DNA ploidy status, LOH and MSI of 11q13 and 1p between benign and malignant pheochromocytomas, and to find the marker or markers useful in distinction between benign and malignant pheochromocytoma or for predicting the malignant potential of this tumor. METHODS: Twenty-two cases of clinically documented benign and malignant pheochromocytomas from the files of Peking Union Medical College Hospital were analyzed. Aside from histological study, Ki-67, p53, CgA, S-100, PCNA and survivin immunohistochemistry studies were performed. DNA ploidy status was assessed by flow cytometry on cell suspensions prepared from formalin-fixed, paraffin-embedded sections. Twelve tumors (7 benign and 5 malignant) with paired normal tissues were microdissected. Tumor and normal tissue DNA were extracted. The obtained DNAs and 8 microsatellite markers related to 11q13 and 1q were subjected to PCR amplification for analysis of LOH and MSI. RESULTS: None of the tumors showed atypical mitosis, only 1 malignant tumor had a mitotic count > 1/10 HPF (2.3/10 HPF). Two malignant tumors exhibited confluent necrosis. Ki-67 index was low in benign tumors (average 0.73%), and high in malignant tumors (average 2.4%). The difference of Ki-67 index between benign and malignant tumors was statistically significant. DNA ploidy status did not correlate with malignancy. Although LOH and/or MSI of 11q13 and 1p were observed in several tumors, a statistically significant difference could not be reached due to the small number of tumors analyzed. CONCLUSION: Only Ki-67 index (> 3%) is an useful marker for distinguishing benign from malignant or for predicting the malignant potential of pheochromocytoma.
Adrenal Gland Neoplasms↗
[Thyrotropin-secreting pituitary adenoma:a clinicopathological analysis of seven cases].
OBJECTIVE: To study the clinicopathological features of thyrotropin-secreting pituitary adenoma (TSH adenoma). METHODS: Clinical and pathological features of 7 TSH adenoma cases were studied by review of patients' medical records, light and electronic microscopy, and immunohistochemistry. RESULTS: All seven patients presented with clinical hyperthyroidism and high levels of plasma free T3, free T4, total T3 and total T4. The levels of TSH failed to be suppressed by thyroxin administration. MRI showed macro or giant pituitary adenomas in all seven patients with tumor diameters ranging from 2.0 to 5.0 cm. Under light microscope, there were 5 cases of chromophobe cell adenoma, 1 case of acidophil cell adenoma, and 1 case of mixed acidophil and chromophobe cell adenoma. Immunohistochemical stains showed a strong positivity of TSH in all the tumors, PRL positive cells in 1 tumor, GH positive cells in 2 tumors and scattered GH and PRL double positive cells in 3 tumors. Ki-67 proliferation index ranged from 0 approximately 0.4%. P53 immunostain was negative in all tumors. After initial surgery, 2 cases had recurrences. However, the Ki-67 proliferation index was not elevated in these two tumors. CONCLUSIONS: The histological features of TSH pituitary adenomas are heterogeneous with chromophobe as the most common subtype. Secretion of TSH was detected by immunohistochemistry in all cases. P53 mutation is not a feature of TSH adenoma and the proliferation marker, such as Ki-67, may not predict clinical behavior of the tumor. Recurrence is likely due to incomplete resection.
Adenoma↗
[Ovarian tumors with endocrine function].
OBJECTIVE: To analyze the clinicopathological features of ovarian tumors with endocrine function. METHODS: Twenty-four cases of ovarian tumor with endocrine manifestation were collected from the hospital. Their clinical presentation and histopathologic features were reviewed, along with a panel immunohistochemistry stainings (EnVision method). The antibodies were AE1/AE3, epithelial membrane antibody (EMA), alpha-inhibin, calretini and smooth myoglobin (SMA). RESULTS: The main clinical endocrinological manifestations were related to an excess production of sex steroids. Histologically, the principle histological subtype of these tumors was ovarian sex cord-stroma tumors, including 13 cases ovarian type (8 granulosa cell tumors, 2 thecofibromas, 3 sclerosing stromal tumors), 7 cases testicular type (1 sertoli cell tumors, 5 sertoli-Leydig cell tumors, 1 Leydig cell tumor, and 2 cases of steroid cell tumor (NOS). Another 2 cases were ovarian epithelial tumors. Grossly, 50% (11/22) ovarian sex cord-stromal tumors were less than 5 cm in diameter. However, 4 tumors were quite larger, up to 18 cm in diameter. Most of these tumors were solid or solid-cystic and their cut surfaces were brown, pink, yellow or grey in color. The 2 primary ovarian epithelial tumors were larger, being 12 cm and 14 cm in diameter, respectively. Immunohistochemically, ovarian sex cord-stromal tumors showed positive staining for alpha-inhibin in all cases (22/22) and for calretinin in majority cases (18/22), and that the intensity of reactivity correlated with the degree of tumor differentiation. The non-neoplastic, luteinized stromal cells in 2 ovarian primary epithelial tumors also showed positive staining. Five cases of fibrothecomas and sclerosing stroma tumors were all positive for SMA. Although 6 of the 22 ovarian sex cord-stromal tumors were AE1/AE3 positive, all were EMA negative. CONCLUSIONS: Most endocrinological syndromes in ovarian neoplasia reflect an overproduction of sex steroids, but the clinical manifestations do not correlate with the tumor histological subtypes. Most functional ovarian tumors are sex cord-stromal tumors and are usually of small to medium in size, but few are larger or giant. The size of the tumor does not correlate with the duration and the degree of clinical manifestations. Ovarian tumors of non-sex cord-stromal type may also be clinically functional. The immunohistochemical results suggests that alpha-inhibin and/or calretinin expression are useful markers in support of a diagnosis of sex cord-stromal tumor of the ovary. Although some of these tumors are AE1/AE3 positive, EMA negativity may be useful for the differential diagnosis with epithelial ovarian tumors.
Adolescent↗
[Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion].
OBJECTIVE: To assess the clinicopathological features of atypical cystic duct (ACD) as a precancerous lesion of the breast. METHODS: Whole mammary gland serial sections were performed on 200 cases of breast cancer without pre-operative biopsy (prior operation, fine needle aspiration or needle biopsy were routinely performed in each case). The clinicopathological findings and immunohistochemical features of ACD were investigated. RESULTS: Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P=0.001). A number of ACD lesions displayed a histological transition to adjacent ductal carcinoma in-situ. In 16 of 44 (36%) patients with ACD, carcinoma cells stained positive for p53. In 12 of these 16 cases (75%), ACD cells also stained positive for p53 protein (P=0.001). Myoepithelial cells of ACD appeared attenuated and stained strongly for alpha-smooth muscle actin. There was no correlation between the ACD-present group and the ACD-absent group in tumor size, nodal metastasis, and immunostaining patterns of estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2 and Ki-67 labeling index of cancerous tissues. All 44 ACD lesions showed a negative staining of c-erbB-2, regardless of the staining result in their corresponding carcinomas. The mean Ki-67 labeling index of ACD lesions was low. CONCLUSIONS: ACD is frequently associated with breast cancer. It may represent a precancerous mammary lesion, supported by the frequent histological continuum between ACD and malignancy, and simultaneous p53 over-expression present in both ACD and its corresponding breast carcinoma.
Biomarkers, Tumor↗
[Detection of Y chromosome loss by fluorescence in situ hybridization in pancreatic cancer].
OBJECTIVE: To investigate the correlation between loss of Y chromosome and development of pancreatic cancer. METHOD: The status of Y chromosome was analyzed by two color interphase fluorescence in situ hybridization. performed on paraffin sections of pancreatic cancer tissues from 15 Chinese males. The probes located on the heterochromatin region of chromosome Y (maps to Yq12) and on the alpha satellite of X chromosome (maps to centromeric region) were selected for testing and as control respectively. RESULTS: The cancer cells from 10 out of the 15 pancreatic cancer patients studied showed loss of chromosome Y. The Y chromosome in the cells of surrounding non-neoplastic pancreatic tissues was intact. CONCLUSIONS: Loss of chromosome Y occurs non-randomly in tumor cells of Chinese male patients with pancreatic cancer. This cytogenetic aberration, which happens in high frequency, may serve as one of the markers for pancreatic malignancy.
Adenocarcinoma↗
[Infection of Penicillium marneffei].
OBJECTIVES: To elucidate the etiology, pathohistology, clinical characteristic and differential diagnosis, reduce missed diagnosis and improve the early detection and treatment of Penicillium Marneffei infection, by means of this case report and literature review. METHODS: A patient hospitalized Penicillium Marneffei infection were presented here, together with 27 cases in the literature, among which 10 patients had complications of AIDS and 5 with other diseases. RESULTS: Penicillium Marneffei is a temperature-sensitive, two-phase fungus, which can infect healthy and immunocompromised subjects. The common symptoms are lymphadenopathy and infection of the lung. The infection may be local or diffuse, involving the intestinal tract, soft tissue, bone, liver, spleen and bone marrow etc. The lesion can be classified into the granuloma type, suppurative type and anergy/necrosis type histologically. The yeast-like fungus were mainly found in the cytoplasm of macrophages, which were demonstrated by PAS and Giemsa staining. The wine red color developed on the culture confirms the diagnosis. CONCLUSIONS: The diagnosis of Penicillium Marneffei infection should be considered when tuberculosis is suspected but not confirmed, and if the patient has a history of having lived or traveled in Southeast Asia, is anemic or resistant to anti-tuberculosis treatment. The major differential diagnosis is histoplasmosis. Early administration of anti-fungus drugs is essential for recovery.
AIDS-Related Opportunistic Infections↗
Association between HLA class II gene and susceptibility or resistance to chronic hepatitis B.
AIM: To investigate the association between the polymorphism of HLA-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B. METHODS: HLA-DRB1, -DQA1 and -DQB1 alleles in 54 patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique. RESULTS: The allele frequency of HLA-DRB1*0301 in the chronic hepatitis B group was markedly higher than that in the normal control group (17.31% vs 5.67%), there was a significant correlation between them (chi2=12.3068, Pc=0.0074, RR=4.15). The allele frequency of HLA-DQA1*0501 in the chronic hepatitis B group was significantly higher than that in the normal control group (25.96% vs 13.68%), there was a significant correlation between them (chi2=9.2002, Pc=0.0157, RR=2.87). The allele frequency of HLA-DQB1*0301 in the chronic hepatitis B group was notably higher than that in the normal control group (35.58% vs 18.87%), there was a significant correlation between them (chi2=15.5938, Pc=0.0075, RR=4.07). The allele frequency of HLA-DRB1*1101/1104 in the chronic hepatitis B group was obviously lower than that in the normal control group (0.96% vs 13.33%), there was a significant correlation between them (chi2=11.9206, Pc=0.0145, RR=18.55). The allele frequency of HLA-DQA1*0301 in the chronic hepatitis B group was remarkably lower than that in the normal control group (14.42% vs 30%), there was a significant correlation between them (chi2=8.7396, Pc=0.0167, RR=0.35). CONCLUSION: HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0301 are closely related with susceptibility to chronic hepatitis B, and HLA-DRB1*1101/1104 and HLA-DQA1*0301 are closely related with resistance to chronic hepatitis B. These findings suggest that host HLA class II gene is an important factor determining the outcome of HBV infection.
Acute Disease↗
Retroviral Vector-mediated Expression of Human Thyimidine Phosphorylase in Pancreatic Carcinoma Cells.
The level of human thymidine phosphorylase (TP) activity increased in several types of malignant tumors, but little was known about its physiological functions. A recombinant retroviral vector expressing TP was constructed and transferred into pancreatic carcinoma cells PC-2. The integration and expression of exogenous TP gene in the transduced cells was verified by PCR, Southern and Northern blotting, and in situ hybridization. The level of TP activity in TP-positive cells was 40- to 70-fold higher than that of parental PC-2 cells. However, there was no significant difference in cell growth and in (3)H-TdR incorporation rate between the transduced and parental cells. These results indicate that TP-expressing cell line has been successfully established, offering an excellent model system for studying the role of TP in cancer cell proliferation and seeking its specific substrates.
Journal Article↗