[Analysis of HER2 gene amplification and its protein expression in 165 cases of breast carcinoma: comparison of chromogenic in-situ hybridization and immunohistochemistry].

OBJECTIVE: To evaluate the sensitivity and specificity of chromogenic in-situ hybridization (CISH) in detecting HER2 gene amplification in breast carcinomas. METHODS: HER2 oncogene amplification and its protein expression in 165 cases of breast carcinoma were investigated by immunohistochemistry (IHC) and CISH. RESULTS: (1) CISH did not detect HER2 gene amplification in 107 cases of IHC negative tumors and 24 cases of IHC 1+ tumors. (2) CISH identified high copy numbers of HER2 gene amplification in 21/22 (95.5%) cases with IHC 3+. (3) In 12 HIC 2+ cases, CISH identified 3 cases of high copy number amplification, 6 cases of low copy number amplification and 3 cases without amplification. CONCLUSIONS: HER2 gene amplification detection by CISH is highly sensitive and has a high concordance with IHC detection of the protein expression. It is concluded that CISH is a tool to evaluate HER2 gene status in breast cancer and can be an implement in conventional pathology laboratories.

[Clinicopathologic analysis and expression of cyclin D1 and p53 of ovarian borderline tumors and carcinomas].

OBJECTIVE: To study the clinicopathological features and expression of cyclin D1 and p53 in epithelial ovarian tumors, and to investigate the correlation between pathogenesis of ovarian cancer and epithelial borderline tumors. METHODS: Fifty four cases of ovarian borderline tumors and 45 cases of ovarian carcinomas from the People's Hospital, Peking University were reviewed retrospectively. The clinical data and pathological findings were analyzed. Immunohistochemical study of cyclin D1 and p53 was performed in all 99 cases. RESULTS: (1) In borderline tumors, the age of patients ranged from 14 - 82 (mean age = 42.5) years. International Federation of Gynecology and Obstetrics (FIGO) stage of borderline tumors was stage I in 48 cases, stage II in 3 cases, and stage III in 3 cases. In ovarian carcinomas, the age of patients ranged from 26 - 80 (mean age = 53.5) years. FIGO stage of carcinoma was stage I in 6 cases, stage II in 8 cases, stage III in 26 cases, and stage IV in 5 cases. In follow-up of 54 cases with borderline tumors the 5-year survival rate was 98% and of 45 cases with carcinomas a 5-year survival rate of 51% was noted. (2) In 54 cases of borderline tumors, mucinous types accounted for 56% (30/54) and serous types accounted for 30% (16/54). There were 5 cases with micropapillary pattern, 3 cases with peritoneal implants, 3 cases with lymph node involvement, 6 cases with microinvasion, one case with intraepithelial carcinoma, and one case with mural nodules. In 45 cases of carcinomas, serous carcinoma was the most (49%, 22/45). The remainder included 3 cases of mucinous types, 8 cases of endometrioid types, 6 cases of transitional cell types, 3 cases of mixed phenotype and 3 cases of undifferentiated types. (3) Overexpression of cyclin D1 and p53 was observed in 31% (14/45) and 56% (25/45) of ovarian carcinomas, respectively. There was a significant association between p53 overexpression and tumor grade. In the borderline tumor group, 69% (37/54) had overexpression of cyclin D1 and 6% (3/54) had overexpression of p53. There were significant differences in expression of cyclin D1 and p53 between conventional serous borderline tumors and high-grade serous carcinomas (cyclin D1: 91% vs 26%; p53: 0 vs 58%). However, micropapillary serous borderline tumors and low-grade serous carcinomas showed remarkably similar expression of cyclin D1 and p53. CONCLUSIONS: Epithelial ovarian borderline tumors are distinct from ovarian cancer in clinical progress and prognosis, and histological types. Overexpression of cyclin D1 is common in ovarian borderline tumors and low grade carcinomas. And overexpression of p53 is more common in high grade ovarian carcinomas. Conventional serous borderline tumors are distinct from high-grade serous carcinomas in pathogenesis. Micropapillary serous borderline ovarian tumors may be closely related to low grade serous carcinomas.

[Expression of estrogen receptor alpha and beta subtypes in the vaginal wall of women with anterior vaginal prolapse].

OBJECTIVE: To observe the expression of estrogen receptor (ER) alpha and ERbeta in the vaginal wall of women with anterior vaginal prolapse, and to investigate the relationships of ER subtypes with the development of pelvic organ prolapse (POP). METHODS: Seven premenopausal women and 33 postmenopausal women with anterior vaginal prolapse who underwent surgery in our hospital from July 1999 to July 2004 were analyzed. Nine premenopausal and 8 postmenopausal women with squamous carcinoma of cervix who underwent surgery served as controls. The expression of ERalpha and ERbeta in squamous epithelium (SE), lamina propria (LP) and muscular layer (ML) of anterior vaginal wall were studied by immunohistochemical staining. RESULTS: (1) Both ERalpha and ERbeta were expressed in SE, LP, ML of vaginal wall of premenopausal and postmenopausal women. (2) The expression of ERalpha was not significantly different in premenopausal and postmenopausal women; the expression of ERbeta was not significantly different in premenopausal and postmenopausal women with POP; however, it was decreased in postmenopausal women without POP (P < 0.05). (3) The expression of ERbeta was significantly higher in postmenopausal POP group than in postmenopausal control group (P < 0.05). The expression of ERalpha was not significantly different in postmenopausal control and postmenopausal POP group. CONCLUSIONS: ERalpha and ERbeta are expressed in vaginal wall of premenopausal and postmenopausal women. In vaginal wall of postmenopausal women with POP, the expression of ERbeta is not decreased; on the contrary, it is increased compared with that of postmenopausal control. ERalpha is not changed significantly.

[Clinicopathologic analysis of 141 cases of metastatic carcinoma in bone].

OBJECTIVE: To study the clinicopathologic features of metastatic carcinoma in bone and to evaluate the role of immunohistochemistry in delineation of possible primary sites. METHODS: One hundred and forty-one cases of metastatic carcinoma in bone encountered during the period from 1998 to 2004 in People's Hospital, Peking University, were reviewed retrospectively. The clinical information, radiographic features and pathologic findings were analyzed. Immunohistochemical study for antigens including cytokeratins, prostatic specific antigen, thyroglobulin, thyroid transcription factor 1 and gross cystic disease fluid protein 15, was performed in 51 cases possessing skeletal metastasis with unknown primary. RESULTS: Skeletal metastasis occurred more commonly in males (male to female ratio = 1.7:1). The age of patients ranged from 23 to 86 years (mean age = 56.5). The presenting symptoms included pain and dysfunction in the affected bones. The locations of skeletal metastasis were as follows: spine (58), pelvic bone (46), long bone (34) and others (3). Twenty-three cases harbored multiple bony lesions. Radiographically, 99 cases (70.2%) of skeletal metastasis were detected by X-rays, including 85 cases (85.9%) showing lytic changes. The primary sites of the tumor could be determined by clinicopathologic correlation in 90 cases (63.8%) and were unknown in the remaining 51 cases. Upon immunohistochemical study, the primary sites were determined in another 40 cases. Overall, the primary sites were identified in 130 cases (92.2%), which included lung (37), female genital system and breast (25), kidney (18), gastrointestinal system (17), liver (12), thyroid (11), prostate (7), bladder (2) and skin (1). CONCLUSIONS: Skeletal metastasis occurs more often in elderly males. Axial bones (spine and pelvis) are usually affected. Lung and female genital system are frequent the primary sites. Immunohistochemical study is useful in cases with occult primary.

[The prognostic value of human neuroendocrine clone on colorectal carcinoma].

OBJECTIVE: To demonstrate the prognostic value of neuroendocrine clone on colorectal carcinoma. METHODS: The immunochemistry methods were used to investigate the percent of neuroendocrine carcinoma in 73 human colorectal carcinoma. Retrospective analysis and follow-up were carried out in all patients. RESULTS: In all 73 cases of colorectal carcinoma, the total percentage of neuroendocrine carcinoma was 17.8%. Neuroendocrine carcinoma included 11 synapse positive, 6 chromogranin positive and 4 both positive. The major factors related to the prevalence of neuroendocrine carcinoma were sex, age, tumor location and Dukes' stage. And the 1-year survival rate of the patients who suffered from neuroendocrine carcinoma is obviously lower than that of other colorectal carcinoma. CONCLUSIONS: The neuroendocrine carcinoma is a special kind of human colorectal carcinoma, and neuroendocrine clone may be a new marker of the malignant potency. The neuroendocrine clone has its prognostic value and may be a novel therapeutic target.

Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer.

AIM: To investigate the expression of mitogen-activated protein kinases (MAPKs) and its upstream protein kinase in human gastric cancer and to evaluate the relationship between protein levels and clinicopathological parameters. METHODS: Western blot was used to measure the expression of extracellular signal-regulated kinase (ERK)-1, ERK-2, ERK-3, p38 and mitogen or ERK activated protein kinaseMEK-1 proteins in surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 42 patients. Immunohistochemistry was employed for their localization. RESULTS: Compared with normal tissues, the protein levels of ERK-1 (integral optical density value 159 526+/-65 760 vs 122 807+/-65 515, P = 0.001), ERK-2 (168 471+/-95 051 vs 120 469+/-72 874, P<0.001), ERK-3 (118 651+/-71 513 vs 70 934+/-68 058, P<0.001), P38 (104 776+/-51 650 vs 82 930+/-40 392, P = 0.048) and MEK-1 (116 486+/-45 725 vs 101 434+/-49 387, P = 0.027) were increased in gastric cancer tissues. Overexpression of ERK-3 was correlated to TNM staging (average ratio of integral optic density (IOD)(tumor): IOD(normal) in TNM I, II, III, IV tumors was 1.43+/-0.34, 5.08+/-3.74, 4.99+/-1.08, 1.44+/-1.02, n = 42, P = 0.023) and serosa invasion (4.31+/-4.34 vs 2.00+/-2.03, P = 0.037). In poorly differentiated cancers (n = 33), the protein levels of ERK-1 and ERK-2 in stage III and IV tumors were higher than those in stage I and II tumors (2.64+/-3.01 vs 1.01+/-0.33, P = 0.022; 2.05+/-1.54 vs 1.24+/-0.40, P = 0.030). Gastric cancer tissues with either lymph node involvement (2.49+/-2.91 vs 1.03+/-0.36, P = 0.023; 1.98+/-1.49 vs 1.24+/-0.44, P = 0.036) or serosa invasion (2.39+/-2.82 vs 1.01+/-0.35, P = 0.022; 1.95+/-1.44 vs 1.14+/-0.36, P = 0.015) expressed higher protein levels of ERK-1 and ERK-2. In Borrmann II tumors, expression of ERK-2 and ERK-3 was increased compared with Borrmann III tumors (2.57+/-1.86 vs 1.23+/-0.60, P = 0.022; 5.50+/-5.05 vs 1.83+/-1.21, P = 0.014). Borrmann IV tumors expressed higher p38 protein levels. No statistically significant difference in expression of MAPKs was found when stratified to tumor size or histological grade (P>0.05). Protein levels of ERK-2, ERK-3 and MEK-1 in metastatic lymph nodes were 2-7 folds higher than those in adjacent normal mucosa. The immunohistochemistry demonstrated that ERK-1, ERK-2, ERK-3, p38 and MEK-1 proteins were mainly localized in cytoplasm. The expression of MEK-1 in gastric cancer cells metastasized to lymph nodes was higher than that of the primary site. CONCLUSION: MAPKs, particularly ERK subclass are overexpressed in the majority of gastric cancers. Overexpression of ERKs is correlated to TNM staging, serosa invasion, and lymph node involvement. The overexpression of p38 most likely plays a prominent role in certain morphological subtypes of gastric cancers. MEK-1 is also overexpressed in gastric cancer, particularly in metastatic lymph nodes. Upregulation of MAPK signal transduction pathways may play an important role in tumorigenesis and metastatic potential of gastric cancer.

[Clinicopathological study of intermediate trophoblastic non-tumor lesions: exaggerated placental site and placental site nodule].

OBJECTIVE: To investigate the clinicopathological features of intermediate trophoblastic non-tumor lesions, and to evaluate the position of immunohistochemistry in differential diagnoses. METHODS: Clinical presentation and morphological study of 15 cases of exaggerated placental site (EPS) and 4 cases of placental site nodule or plaque (PSNP) were reviewed. Immunohistochemical stains for hCG, hPL, inhibin-alpha, PLAP, CK18 and Ki-67 were performed. RESULTS: The age of patients ranged from 25 to 40 years with an average of 31.5 years for EPS and 26 to 39 years with an average of 34.3 years for PSNP. Microscopically, EPS was characterized by cords and small sheets of implantation site intermediate trophoblasts infiltrating the endometrium, myometrium and arterial walls. The general histological structures of the endometrium and myometrium were preserved. PSNP was characterized by multiple circumscribed nodular lesions consisting of so-called chorionic-type intermediate trophoblasts and hyaline-like matrix present in the endometrium. Immunohistochemical stainings for hPL and CK18 were positive in the 15 EPS cases. Immunoreactivity for CK18, Inhibin-alpha and PLAP was detected in 4 PSNP cases. The Ki-67 labeling index in 15 EPS cases was low (< or = 5%), while Ki-67 index in 4 PSNP cases was close to 0. CONCLUSIONS: The clinical presentation and pathological features of EPS and PSNP differ from those of trophoblastic tumors (placental site trophoblastic tumor, epithelioid trophoblastic tumor and choriocarcinoma). Immunochemical staining is of great value in their differential diagnoses.

[Study on the resistance of methicillin-resistant staphylococcus aureus to iodophor and chlorhexidine].

OBJECTIVE: To study the resistance of methicillin-resistant staphylococcus aureus (MRSA), an indicator used in hospitals. METHODS: We used minimal inhibitory concentrations (MIC) of iodoph and chlorhexidine to MRSA, methicillin-sensitive staphylococcus aureus (MSSA) and staphylococcus aureus ATCC6538. RESULTS: Obvious difference between MRSA and MSSA the MIC of Iodophor was noticed. Among MICs, 5.3% MRSA strains were 2-folds and 28.9% MRSA strains were 1.5 fold more than staph. aureus ATCC6538, while the MIC of 11.1% MSSA strains raised 1.5 fold than ATCC6538. The MIC of 83.3% MSSA strains were the same to staph. aureus ATCC6538. The MIC of chlorhexidine to MRSA, MSSA and staphylococcus aureus ATTC6538 were similar to each other. CONCLUSION: Results showed that some MRSA were more resistant to Iodophor than staph. aureus ATCC6538, but remained the same resistance to Chlorhexidine. Thus the concentration of Iodophor should be raised when the resistant strains were isolated.