MIB1 proliferation index in breast infiltrating carcinoma: comparison with other proliferative markers and association with new biological prognostic factors

AIMS: In breast invasive carcinoma our objectives were I) to compare cellular proliferation determined by MIB1 index with S-phase fraction (SPF) assessed by flow cytometry and with mitotic index, and II) to examine the association of MIB1 index with classical and with new biological prognostic factors [bcl-2, p53, c-erbB-2 and cathepsin D (CD)]. METHODS AND RESULTS: From 102 cases of breast invasive carcinoma, 5-microm thick serial sections were cut from formalin-fixed, paraffin-embedded tissue blocks, and processed for detection of CD, c-erbB-2, p53, bcl-2, Ki-67 antigen MIB-1 and estrogen receptors (ER) and progesterone receptors (PR). SPF was measured by flow cytometry in fresh-frozen tissue samples taken from the carcinoma in each patient. MIB1 index was correlated with SPF (rho=0.45, p<0.0001) and with mitotic index (rho=0.42, p<0.0001). The MIB-1 index was positively associated with the histological grade (p=0.001), tumor size (p=0.04) and the presence of metastases in axillary lymph nodes (p=0.01). MIB1 was associated directly with p53 (p=0.045) and inversely with bcl-2 (p=0.0002). The MIB-1 index was not statistically associated with c-erbB-2. There was a weak association between MIBI index and stromal cell CD. The median MIB1 index was higher in tumors with moderate to strong CD staining of stromal cell, but the difference did not reach statistical significance (p=0.09). CONCLUSIONS: MIB1 index correlates with well established methods for assessing tumor proliferation and with parameters of an aggressive phenotype of tumor. MIB1 index is an effective and readily accessible method for assessing tumor proliferation in breast carcinoma.     

The assessment of multiple variables on breast carcinoma fine needle aspiration (FNA) cytology specimens: method, preliminary results and prognostic associations

The assessment of multiple variables on breast carcinoma fine needle aspiration (FNA) cytology specimens: method, preliminary results and prognostic associations
We have assessed multiple biological variables on breast carcinoma FNA specimens using a Cytoblock technique. The growth fraction (MIBI), oestrogen receptor (ER), progesterone receptor (PR), p53 mutant protein, c-erbB-2, epidermal growth factor receptor (EGFR), NCRCl Vepithelial membrane antigen (EMA) and DNA plopidy were examined. Objective quantification using image analysis (CAS 200) was applied as appropriate. Fifty cases were examined in this preliminary study. Excellent correlation between the Cytoblock preparations and parallel tissue sections was seen. Of the cancers, 81% were aneuploid with only 19% diploid in character, but 67% of the carcinomas were of histological grade 3. The mean nuclear area staining with MIBl was 31.3% and with ER was 26.7%. Twenty-four percent (24.1%) of the nuclear area showed immunoreactivity with PR. Significant immunostaining was seen in 38%, 46%, 38% and 95% of carcinomas with c-erbB-2, p53, EGFR and EMA, respectively. A significant association between histological grade of the resected tumours and both MIBl (P=0.04) and EGFR (P=0.02) expression in the Cytoblock samples was seen. p53 (P = 0.03) and EGFR (P=0.01) immunoreactivity showed an association with tumour size. EGFR (P=0.04) immunostaining also showed a relationship with the lymph node status of the patient. The technique is, we believe, a useful one for the assessment of multiple variables on breast cytology specimens; these preliminary data suggest that some of these may be useful in predicting prognosis in breast cancer patients.     

Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.     

Immunohistochemical localization and correlation of p53 and PCNA expression in breast carcinoma

The object of the present study is to detect the p53 tumour suppressor gene and proliferation cell nuclear antigen (PCNA) expression in breast carcinoma by immunohistochemistry and correlate them with the prognostic parameters. Total 35 cases of primary breast carcinoma were studied and classified histologically. Paraffin sections were stained by using monoclonal antibody D07 for p53 protein and PC-10 for PCNA. Out of 35 cases, 16 (45.7%) were p53 positive and 25 (71.4%) were PCNA positive. The mean PCNA labelling index (PCNA LI +/- SD) was 58.97 +/- 22.72 in tumors positive for both p53+ and PCNA+ while cases negative for p53- and positive for PCNA+ has higher PCNA LI +/- SD (59.24 +/- 18.97). The difference in the two groups was not significant. Most cases were positive for both p53+ and PCNA+ in the age group < 30 with higher mean PCNA LI +/- SD (62.20 +/- 27.13) than in the group > 30 (57.88 +/- 18.47). In the pre-menopausal group 57.1% cases were positive for p53+ with higher PCNA LI +/- SD (59.94 +/- 24.22). Maximum p53 and PCNA positivity was observed in grade III tumors (63.2% and 84.2%). The mean PCNA LI +/- SD was also highest in grade III carcinomas (66.83 +/- 13.97). No significant correlation was found between p53 and PCNA status with morphological type and tumour size except that logistic regression showed a positive correlation with tumour grade. Therefore the present study suggests that both p53 expression and PCNA are markers of poor differentiation in breast cancer.     

Fibrin sealant does not decrease seroma output or time to drain removal following inguino-femoral lymph node dissection in melanoma patients: A randomized controlled trial (NCT00506311)

Background

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases.

Patients and methods

This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status.

Results

The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002).

Conclusion

HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.     

The expression of PCNA, c-erbB-2, p53, ER and PR as well as atypical hyperplasia in tissues nearby the breast cancer

To examine the proper margin for breast conservative surgery in Chinese women population. 40 breast cancer specimens were collected and each sample was dissected into several groups: primary tumor group, 1 cm paracarcinoma, 2 cm paracarcinoma, 3 cm paracarcinoma and excessive 3 cm paracarcinoma groups. The immunohistochemistry staining was performed to measure the expression levels of proliferating cell nuclear antigen (PCNA), c-erbB-2, p53, estrogen receptor (ER) and progesterone receptor (PR). The gene expressions of PCNA, c-erbB-2, and p53 gradually decreased with the increased distance from primary tumor (P < 0.05). The 1 and 2 cm paracarcinoma group (no differences between the two, P > 0.05) showed higher risk factors (c-erbB-2, p53) than the 3 cm and excessive 3 cm paracarcinoma groups (P < 0.05). The expression of PCNA, ER, and PR showed no correlation with cancer progression (P > 0.05). Beyond the paracarcinoma 2 cm distance, the tissues showed significant decreases in tumor gene expression, which could represent the appropriate region for breast conservative surgery.     

Immunohistochemical expression of retinoblastoma gene product (Rb), p53 protein, MDM2, c-erbB-2, HLA-DR and proliferation indices in human urinary bladder carcinoma

Archival biopsy specimens from transitional cell bladder cancers (n=88) were analysed immunohistochemically for the expression of the retinoblastoma (Rb) gene protein, p53, mdm2, c-erbB-2, HLA-DR antigen and proliferation indices. An altered nuclear expression of Rb, p53 and mdm2 was observed in 55.2%, 33.3% and 18.2% of tumors respectively. Cytoplasmic membrane immunoreactivity (>25% tumor cells) for c-erbB-2 was detected in 14.1% of tumors and aberrant HLA-DR antigen cytoplasmic staining (>5% of tumor cells) in 22.2% of the cases. P53 overexpression was associated with higher tumor grade and stage. Aberrant HLA-DR antigen expression and PCNA were also correlated with the grade of differentiation and tumor stage. MIB1 was statistically correlated with stage. pRb scores and HLA-DR antigen expression were correlated with proliferation activity as determined by PCNA and MIB1 immunostaining. p53 protein was also strongly correlated with the proliferation index PCNA. A strong correlation between PCNA and MIB1 (p<0.0001) was also found. In addition a statistically positive correlation between p53 and HLA-DR antigen expression was observed. Our data show that, although pRb and p53 protein expressions are not associated between them, they may contribute to the growth fraction of the bladder cancer. In addition, p53 and HLA-DR antigen expression could be indicators of aggressive behavior of bladder cancer.     

人乳腺癌细胞p53和bcl-2蛋白的表达状况及与激素受体的关系

为了进一步证明 p5 3和 bcl- 2癌基因蛋白的反向关系 ,我们用 SP法进行免疫细胞化学染色 ,观察了 p5 3、 bcl- 2、雌激素受体 (estrogen receptor,ER)、孕激素受体 (progesterone receptor,PR)在人乳腺癌细胞系 MCF7和 MDA- MB2 31中的表达情况 ,并应用图像分析系统对其阳性反应物进行定量。结果 :MCF7细胞表达 ER和 PR,而 MDA- MB2 31细胞不表达。二个细胞系均表达 p5 3,但 MCF7光密度 (OD)值为 0 .10 0 9± 0 .0 14,而 MDA- MB2 31细胞为 0 .16 78± 0 .0 42 ,后者明显高于前者 (P<0 .0 0 0 1)。二系细胞均可见到 bcl- 2阳性物质 ,但 MCF7表达的 OD值为 0 .10 45± 0 .0 2 0 8,而 MDA- MB2 31细胞仅为 0 .0 5 2 5± 0 .0 113(P<0 .0 0 0 1)。表明 bcl- 2的表达与 ER及 PR的存在有很强的相关性 ,并且与 p5 3的表达呈明显的相反关系     

Image cytometric bcl-2:bax and bcl-2:bcl-x ratios in invasive breast carcinoma: correlation with prognosis

BACKGROUND: The bcl-2 family of proteins are important regulators of apoptosis. Some of the members, such as bcl-2 and bcl-x(L), inhibit cell death, whereas others, such as bax and bcl-x(S), promote cell death. We evaluated the ratios of bcl-2:bax and bcl-2:bcl-x expression by image cytometry in invasive breast carcinoma to determine prognostic significance. DESIGN: Five-micron sections of formalin-fixed, paraffin-embedded tissue from 88 invasive breast carcinomas were immunostained using steam antigen retrieval, an avidin biotin-complex technique with automated stainer and primary antibodies against bcl-2 (1/160; Dako, Carpenteria, CA), bax (1/1,500; PharMingen, San Diego, CA), and bcl-x (1/1,500; PharMingen). Positive controls were tonsil (bcl-2) and normal breast (bax and bcl-x) tissue samples. Immunostain was measured in 15 high power fields as percentage positive area (PPA) in nuclei and cytoplasm using the CAS 200 image analyzer (Becton Dickinson, San Jose, CA). RESULTS: Median follow-up was 105 months (range 11-130). Significantly improved disease-free survival was found in patients with a bcl-2:bcl-x ratio > or = 1 by univariate and multivariate analyses. The bcl-2:bax ratio was not predictive of overall or disease-free survival. A significant difference in overall and disease-free survival was found between carcinomas with positive and negative bcl-2 expression by univariate analysis; by multivariate analysis, bcl-2 expression was an independent prognostic factor for disease-free survival. The 5-year survival rates were 77% and 50% in patients with bcl-2-positive and bcl-2-negative carcinomas, respectively. CONCLUSION: A bcl-2:bcl-x ratio > or = 1, assessed by image cytometry, is significantly associated with improved disease-free survival in patients with invasive breast carcinoma. Significantly increased overall and disease-free survival is associated with positive bcl-2 expression.     

Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients

In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdr1 gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan–Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further larger studies (validation set as opposed to the training set used in the present study). Due to the complexity of events in cancer, the evaluation of a combination of prognostic factors should be of value to clinicians to make a more objective estimate of the prognosis of individual breast cancer patients.     

Image cytometry of aneuploidy, growth fraction (MoAb Ki-67) and hormone receptors (ER, PR) immunocytochemical assays in breast carcinomas

DNA nuclear content was assessed in human breast carcinomas (n = 132) using image cytometry. Optical density histograms of Feulgen stained cell imprints from fresh tissue samples, subsequently frozen for immunocytochemical assays, were determined by the SAMBA system and used for the DNA index, the ploidy balance (PB) and the proliferation index (PI) computation. The three parameters were correlated to (i) histological data (tumour grade, vascular and/or lymph node invasion) and to (ii) growth fraction (Ki67), hormone receptor antigenic sites (ER, PR) and intramedullar (bone marrow) biopsies and anti-KL1-positive epithelial cells. It was shown that 57% of breast carcinomas were aneuploid. Aneuploidy PI significantly correlated to the criteria of poor prognosis such as high tumour grade, vascular and lymphatic invasion and to increased Ki67-positive cells, and the absence of or low ER and PR. Since image cytometry is easy to handle and perfectly suitable for current diagnostic practice in pathology departments, particularly for tumour cell ploidy assessment and standardized analysis of immunostaining procedures with morphological control of the preparation, we conclude that image cytometry, as performed with the SAMBA, must be regarded as a relevant tool for prognosis evaluation and therapy guidance in individual patients.     

Prognostic markers in histologic and cytologic specimens of breast cancer

OBJECTIVE: To correlate histologic and cytologic specimens of breast cancer by the expression of prognostic factors, such as estrogen receptor (ER), progesterone receptor (PR) and c-erbB-2, with immunochemical staining. STUDY DESIGN: Cytologic and histologic specimens from 83 patients were analyzed for expression of ER and PR, and 30 cases were analyzed for overexpression of c-erbB-2 using a standard immunochemical method. The material used for immunocytochemical staining was taken from the needle and syringe after each aspiration and smear preparation. The material was washed into a small container with preservative solution. Immunohistochemical staining was performed on paraffin-embedded specimens. RESULTS: A significant association was found between the histologic specimens and cytologic specimens by means of the expression of immunochemical markers. The best correlation between cytologic and histologic specimens was found when using c-erbB-2. CONCLUSION: A reliable and rapid evaluation of markers for breast cancer can be achieved by immunocytochemical staining on cytologic material. A good association was found between histologic and cytologic specimens using immunostaining.     

Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.     

Quantitative immunoprofiles of breast cancer performed by image analysis

OBJECTIVE: To determine the biopathologic profiles of breast cancer for greater knowledge of tumor natural history and clinical outcome. STUDY DESIGN: In 99 in situ (ISC) and 2718 infiltrating breast carcinomas (IC), biologic markers (estrogen receptor [ER], progesterone receptor [PR] proliferation index, cerbB-2/NEU, p53, bcl-2 and DNA ploidy) were evaluated with an image analysis system (CAS 200/486). In 105 mixed invasive cancers with size < or = 1 cm, a separate analysis of in situ (ISCm) and invasive component (ICm) was obtained. A clinical study of 836 invasive breast cancers was performed. RESULTS: Different biophenotypes were obtained: among ISCs, cribriform type exhibited biologic behavior similar to that of normal breast tissue (ER+, PR+, proliferation index [PI] low, NEU-, p53-, bcl-2+) the opposite profile was displayed by comedo type, and intermediate phenotypes were observed in noncomedo and lobular types. Comparing ISC and ISCm, PI and p53 expression had the highest levels in ISCm with respect to other groups. NEU overexpression exhibited a decreasing value from ICm to IC. Younger women (< or = 40 years) with IC demonstrated a worse biologic profile (high PI, p53+, ER- and size > 2 cm). In multivariate analysis, PI and NEU in node-negative patients, and NEU, PR and size in node-positive ones emerged as prognostic parameters. CONCLUSION: The results underline the importance of the quantitative biologic profile for defining tumor behavior and patient management.     

磁共振成像表观扩散系数与乳腺浸润性导管癌组织学分级及预后指标的相关性研究

目的:探讨磁共振成像(MRI)表观扩散系数(ADC)与乳腺浸润性导管癌组织学分级及其预后指标的相关性。方法:收集2016年5月至2017年5月于我院就诊的并经手术病理确诊为乳腺浸润性导管癌的患者112例作为研究对象,选取患者乳腺癌组织样本作为病例组,同时选取患者对侧正常乳腺组织样本作为对照组,所有患者均行常规MRI和磁共振扩散加权成像(DW-MRI)检查,分别测量两组样本的ADC值,比较不同乳腺浸润性导管癌组织学分级与正常乳腺组织的ADC值,分析乳腺浸润性导管癌组织的ADC值与肿瘤直径大小、淋巴结转移状态、有无远处转移及雌激素受体(ER)、孕激素受体(PR)和Ki-67表达的关系,并分析ADC值与组织学分级及预后指标的相关性。结果:乳腺浸润性导管癌病理分级I级的ADC值低于对照组,病理分级II级的ADC值低于病理分级I级及对照组,病理分级III级的ADC值低于病理分级II级、I级及对照组,差异均具有统计学意义(P0.05)。乳腺浸润性导管癌患者中,肿块直径2 cm、无淋巴结转移、ER阴性、PR阴性、Ki-67阴性患者的平均ADC值均高于肿块直径≥2 cm、有淋巴结转移、ER阳性、PR阳性、Ki-67阳性患者,差异均具有统计学意义(P0.05);而有无远处转移患者之间比较差异无统计学意义(P0.05)。经Spearman秩相关分析结果显示,乳腺浸润性导管癌患者的ADC值与病理组织学分级呈现负相关关系(rs=-0.716,P=0.000);与肿块直径大小、有无淋巴结转移及ER、PR、Ki-67的表达均呈负相关(rs=-0.316、-0.545、-0.667、-0.598、-0.443,P均0.05),与有无远处转移无相关性(rs=0.091,P=0.887)。结论:乳腺浸润性导管癌的ADC值与癌组织学分级和预后相关指标存在一定相关性,可作为一种临床诊断和判断预后的重要指标,具有重要临床价值。     

c‐erbB‐2 and p53 expression in breast cancer fine needle aspirates

The aim of this study was to co‐evaluate c‐ erbB ‐2 and p53 protein expression in breast cancer fine needle aspirates (FNA) and to compare this with histological variables and the immunohistochemical phenotype of the tumours. Furthermore, we assessed the relationship of c‐ erbB ‐2 and p53 immunocytochemical expression to tumour prognostic factors. We examined 124 breast cancer FNAs and 79 matched surgical specimens using the avidin–biotin complex (ABC) and the alkaline phosphatase immunocytochemical techniques. C‐ erbB ‐2 immunopositivity was detected in 37.9% of the FNAs, while 31.7% were positive for p53. A statistically significant correlation was observed between p53 negativity and absence of c‐ erbB ‐2 immunostaining in the FNAs ( P =0.0007). Smears from infiltrating ductal carcinomas tended to be more frequently positive for p53 (36.7%) than those from lobular carcinomas (11.7%) ( P =0.054). In matched tumour tissues, c‐ erbB ‐2 was positive in 16.7% and p53 in 19% of cases. The immunocytochemical results for both c‐ erbB ‐2 and p53 were significantly correlated with the immunohistochemical results. There was no correlation between c‐ erbB ‐2 and p53 immunostaining, in both FNAs and tissues, and patients' menopausal status, tumour size, grade and lymph node status.     

PCNA and P53 expression in relation to clinicopathological features of oral papilloma

Although papilloma is the most frequent benign epithelial tumour of oral cavity, its biological potential for malignant transformation is still to be evaluated. The aim of the study was to correlate PCNA and P53 expression in 55 oral papillomas with some clinicopathological variables. The tissue samples were stained with H+E and by immunohistochemistry for PCNA and P53 protein. Staining patterns were assessed semiquantitatively and correlated with each other and grade of tumour epithelial dysplasia, tumour size, localization well patient age and sex. PCNA immunostaining was positive 43 (78%) oral papillomas. P53 immunohistochemical reaction was positive in 38 (69%) out of 55 epithelial tumours. Positive relationship between PCNA and P53 expression was observed as well as between PCNA immunostaining and grade of epithelial dysplasia. There was no statistically significant relationships between PCNA, P53 immunohistochemical positivity and papilloma size, site, patient age and sex. The results of this study suggest that immunohistochemical P53 overexpression is valuable marker of early neoplastic transformation and together with PCNA are presumed predictors for malignant transformation of oral papillomas.     

Bcl-2 expression in colorectal tumours. Correlation with p53, mdm-2, Rb proteins and proliferation indices

Immunostaining for bcl-2 protein was performed in 27 colorectal adenomas and 108 colorectal adenocarcinomas. The aim of the study was to determine bcl-2 expression in correlation with p53, mdm-2 and Rb expression, with proliferation indices (Ki-67-LI, PCNA-LI) as well as with conventional clinicopathological variables. A higher proportion of adenomas (30.8%) than carcinomas (16.7%) expressed bcl-2 and conversely, a lower proportion of adenomas (7.4%) than carcinomas expressed p53 (57.1%), the difference being statistically significant (p<0.0001). No correlation of bcl-2 expression with p53 expression (parallel or inverse) as well as with the other parameters studied was observed in any tumour. The bcl-2+/p53- subgroup of cancers showed a trend for correlation with negative lymph node status. Our data suggest, that bcl-2 expression may be involved in the early phase of colorectal carcinogenesis regardless of p53 status, while p53 function may be involved in a late stage of the adenoma-carcinoma sequence. P53 is apparently not involved in the regulation of apoptosis in the colorectal neoplasias or perhaps bcl-2 expression, as an early event in colorectal tumours, may occur before changes of p53 take place. Tumours with bcl-2+/p53- immunophenotype are frequently associated with negative lymph node status and seem to have a less aggressive behavior.     

The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients

Background and Objective

The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value.

Methods

From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated.

Results

There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P = 0.00). There was significant association between bcl-2, and bax expression (P<0.05). p53 expression correlated with histological grade (P = 0.01); bcl-2 expression with pathological stage (P = 0.00); bax expression with male (P = 0.02), histological grade (P = 0.01), Borrmann type (P = 0.01), tumor location (P = 0.00), lymph node metastasis (P = 0.03), and pathological stage (P = 0.03); c-myc expression with Borrmann type (P = 0.00). bcl-2 expression was related with good survival in univariate analysis (P = 0.01). Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P = 0.03).

Conclusion

The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.     

Insulin-like growth factor II (IGF-II) immunohistochemistry in breast cancer: relationship with the most important morphological and biochemical prognostic parameters

Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.