Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression of p53 and c-erbB-2 proteins

Aim : This study (1) investigates the incidence of bcl-2 protein expression in a series of 108 cases of ductal carcinoma in situ (DCIS), including 25 with early invasive carcinoma, and (2) evaluates the relationship of bcl-2 expression to the histological grade of DCIS and to the expression of oestrogen receptor (ER), c-erbB-2 and p53 proteins.  

Methods and results

The expression of bcl-2, oestrogen receptor (ER), c-erbB-2 and p53 proteins was determined immunohistochemically. Cases were regarded as positive for individual antibodies when at least 10% of the DCIS cells showed positive staining. DCIS was graded histologically as well ( n  = 9), intermediately ( n  = 24), or poorly differentiated ( n  = 75). bcl-2 expression was documented in 57 cases (53%) and was strongly associated with the histological grade of DCIS ( P  < 0.0001). All cases of well-differentiated DCIS were bcl-2 positive and loss of bcl-2 expression was almost exclusively confined to poorly differentiated DCIS lesions. bcl-2 expression was also closely associated with positive ER status ( P  < 0.0001). Forty-seven of 57 (82%) bcl-2 positive cases were ER positive while 49/51 (96%) bcl-2 negative cases were ER negative. There was a significant inverse correlation between bcl-2 expression and both p53 protein expression ( P  = 0.0004) and c-erbB-2 expression ( P  < 0.0001). Nineteen of 24 (79%) p53 positive cases and 38/45 (84%) c-erbB-2 positive cases showed loss of bcl-2.  

Conclusions

Loss of bcl-2 expression occurs in poorly differentiated DCIS and is related to negative ER status and to positive p53 and c-erbB-2 status. This pattern of bcl-2 expression and its association with other biological markers in DCIS is similar to that reported in invasive breast carcinoma.     

p53 tumour suppressor gene protein expression in early and advanced gallbladder carcinoma

 

Aims:

Gallbladder carcinoma is one of the most frequent malignant tumours occurring in Chile and the mortality rate in both sexes ranks among one of the highest in the world. Mutation of p53 tumour suppressor gene has been demonstrated in many tumours. Our aim was to determine protein expression of p53 gene in early and advanced gallbladder carcinoma.  

Methods and results:

Protein expression of gene p53 was studied by immunohistochemical means in 191 gallbladder carcinomas (157 primary tumours, 34 metastases) and 25 controls. In 86 out of 191 cases (45%), protein expression of gene p53 was observed. Differences related to sex, age, or race were not observed. All gallbladder controls were negative. Twenty-five per cent of well-differentiated tumours were p53 positive, while moderate or poorly differentiated carcinomas reached 50% ( P  = 0.04). p53 expression was observed in 23.5% of early carcinomas and in 48.2% of advanced carcinomas ( P  = 0.01). No differences between primary tumours and metastasis were demonstrated.  

Conclusions:

Protein expression of p53 tumour suppressor gene is observed in 45% of gallbladder carcinomas. The absence of expression in controls and in normal mucosa adjacent to tumours suggests its utility in differentiating atypical gallbladder epithelia from neoplastic lesions.     

The extent of apoptosis is inversely associated with bcl-2 expression in premalignant and malignant breast lesions

 

Aims:

In this study we investigated the extent of apoptosis in benign, premalignant and malignant breast lesions and its association with the immunohistochemical expression of bcl-2 oncoprotein.  

Methods and results:

In order to detect apoptotic cells and bodies in tissue sections, the 3'-end DNA labelling method was used. Immunohistochemical staining was performed by using the avidin–biotin–peroxidase complex technique. A monoclonal antibody agains bcl-2 oncoprotein was used and the specificity of the antibody was confirmed by immunoblot analysis. According to the results the extent of apoptosis, as determined by the apoptotic index, was lowest in benign ductal hyperplasias and sclerosing adenoses (0.15% and 0.07%, respectively). It was moderately elevated in atypical hyperplasias and in-situ carcinomas (0.20% and 0.40%, respectively) and highest in invasive carcinomas (0.76%). In ductal invasive carcinomas, grade I lesions showed a lower apoptotic index (0.52%) than grade II (0.72%) and grade III (1.17%) carcinomas. The apoptotic index was not significantly lower in lobular (0.82%) than in ductal invasive carcinomas (0.85%). bcl-2 immunohistochemistry was inversely related to the apoptotic index. In all cases studied the inverse association was very strong ( P  = 0.0004) but it was also present when only carcinomas were analysed ( P  = 0.01). In benign and atypical hyperplasias, bcl-2 positivity was observed in all cases, but such cases were less frequent in in-situ lesions and in invasive carcinomas.  

Conclusions:

The results show that there is an inverse relationship between the extent of apoptosis and bcl-2 expression in breast lesions suggesting that its expression affects the regulation of apoptosis in them.     

Apoptosis is associated with atypical or malignant change in meningiomas. An in situ labelling and immunohistochemical study

Aims : Although necrosis is an important phenomenon with implications for grading and prognostication in meningiomas, the alternate form of cell death, apoptosis, has not been extensively studied. In this series, we aimed to determine whether apoptosis in meningiomas correlated with histological types and grading. We also looked for a relationship between expression of apoptosis-related genes bcl-2 , p53 , c-myc and apoptosis in meningiomas.  

Methods and results

Fifty-one meningiomas of diverse histological subtypes and grades were investigated with in-situ end-labelling of DNA fragments as well as immunohistochemical analysis of three apoptosis-related genes: p53 , bcl-2 and c-myc . Our results showed that the apoptosis index was significantly higher in high-grade meningiomas (0.12%, n  = 12) in than the benign meningiomas (0.023%, n  = 39) ( P  = 0.001) but there was no difference among the different histological subtypes of the benign meningiomas ( P  = 0.125). There is no obvious relationship between p53, bcl-2 and c-myc staining and apoptosis index in this group of meningiomas.  

Conclusion

We conclude that apoptosis is an important phenomenon in meningiomas and that it is associated with atypical or malignant changes in meningiomas. Apoptosis in meningiomas has no clearcut relationship with expression of p53 , bcl-2 and c-myc .     

Erythrophagocytic tumour cells in melanoma and squamous cell carcinoma of the skin

 

Aims:

Erythrophagocytosis is a characteristic feature of tumour cells in malignant histiocytosis, some leukaemias, lymphomas, and also reactive histiocytes in the haemophagocytic syndrome associated with a variety of infections and neoplasms. It has also been found exceptionally in metastatic malignant epithelial cells in bone marrow and lymph nodes. We present two cases, a cutaneous malignant melanoma and an acantholytic squamous cell carcinoma, in which erythrophagocytosis by tumour cells was demonstrable by both light and electron microscopy.  

Methods and results:

The melanocytic and squamous nature of these cells was supported by the immunohistochemical detection of HMB45, S100, and NKI-C3 in the former, and cytokeratin and EMA in the latter, and at ultrastructural level by the presence of melanosomes and tonofilaments, respectively.  

Conclusions:

This is, to our knowledge, the first documented report of erythrophagocytic tumour cells in human melanomas and primary carcinomas. Biological considerations apart, this unusual feature can prove to be of value to avoid a misdiagnosis of a variety of haematopoietic malignancies.     

Expression of stratified epithelial-type cytokeratins in hyalinizing trabecular adenomas supports their relationship with papillary carcinomas of the thyroid

 

Aim:

To evaluate the cytokeratin pattern of expression of hyalinizing trabecular adenomas and to verify whether or not these tumours, that share morphological features with papillary carcinomas, present the stratified epithelial-type cytokeratins commonly found in ordinary papillary carcinomas.  

Methods and results:

This study consisted of the immunohistochemical detection of simple and stratified epithelial type cytokeratin filaments in a series of six hyalinizing trabecular adenomas, three papillary carcinomas with a trabecular growth pattern and two carcinomas combining hyalinizing trabecular and papillary patterns. Simple epithelial-type cytokeratins 7, 8, 18 and 19 were found in every case. Expression of the stratified epithelial-type cytokeratins 1, 5/6 and/or 13 was detected in four hyalinizing trabecular adenomas.  

Conclusion:

Based on this, as well as on the cytological features and on the frequent co-occurrence of hyalinizing trabecular adenoma and papillary carcinoma, we suggest that the former lesion may be considered a peculiar encapsulated variant of papillary carcinoma.     

bcl-2 and p53 immunophenotypes in pre-invasive, early and advanced oesophageal squamous cancer

 

Aims:

An inverse correlation between bcl-2 and p53 expression has been reported in several types of epithelial tumour. The role of bcl-2 and p53 in the development of oesophageal squamous carcinoma has yet to be established. The expression of bcl-2 and p53 proteins has been evaluated in the multistage oesophageal tumorigenesis, which progresses from normal mucosa to dysplasia (squamous intraepithelial lesion, SIL), to invasive early and advanced oesophageal squamous cancer.  

Methods and results:

Sixty-four cases of squamous oesophageal cancer, coexisting with SIL in 18 cases, were immunohistochemically analysed for any overexpression of bcl-2 and p53 proteins. Any association of bcl-2 and p53 protein expression with patient survival was also analysed. We observed bcl-2 expression that decreased significantly during the progression of oesophageal carcinogenesis. A decreasing frequency in the expression of bcl-2 in advanced oesophageal squamous cancer coincided with frequent p53 overexpression. bcl-2 expression was correlated with patient survival by univariate analysis. The association disappeared after adjusting for tumour stage. p53 overexpression showed no association with patient survival by either univariate or multivariate analysis.  

Conclusions:

The down-regulation of bcl-2 and up-regulation of p53 in advanced oesophageal squamous cancer suggest that bcl-2 and p53 proteins may interact in the progression of oesophageal squamous cancer.     

Carcinosarcoma of the oesophagus showing neuroendocrine, squamous and glandular differentiation

 

Aim:

A case of oesophageal carcinosarcoma occurring in a previously fit, 64-year-old man is reported.  

Case summary:

The carcinomatous component displayed neuroendocrine, squamous and glandular differentiation; the sarcomatous component showed no specific features of differentiation. In-situ squamous carcinoma was present in the adjacent squamous mucosa. The most superficial part of the invasive tumour consisted of carcinosarcoma with a predominant neuroendocrine epithelial component. Squamous carcinoma without an accompanying sarcomatous component occupied most of the deeper part of the tumour, suggesting outgrowth of this tumour type by a selective growth advantage.  

Conclusion:

We speculate that further tumour growth might have led to complete replacement of the tumour by pure squamous carcinoma, and that other advanced oesophageal squamous carcinomas might have had their origin in a short-lived carcinosarcomatous phase.     

Stereological estimates of the nuclear/cytoplasmic ratio and star volume on fibreoptic biopsies are of prognostic value for survival in a preliminary study of advanced squamous cell carcinoma of the lung

 

Aims:

This study evaluated the role of morphometric and clinical parameters in establishing the prognosis of patients submitted to radiotherapy for advanced squamous cell carcinoma of the lung.  

Methods and results:

Morphometric studies were performed by point counting techniques. Forty patients were included in this study. Group 1 patients ( n  = 22) were those with survival equal to or less than 6 months; group 2 ( n  = 10) patients had a survival of 7 to 12 months; and group 3 ( n  = 8) included patients with survival greater than 12 months. To characterize these three groups of patients, models combining categorical and continuous variables were constructed by means of discriminant analysis. Weight loss, histological grade, nuclear/cytoplasmic ratio and star volume of the nuclei were selected during the backward procedure as relevant variables to characterize the three groups of patients. The overall sensitivity of the model was 90%.  

Conclusions:

Our results indicate that histopathological data may help to predict prognosis in patients with advanced squamous cell lung carcinoma, and encourage the use of morphometric procedures in histopathological analysis of this type of lung tumour.     

Large cell neuroendocrine carcinoma of the thymus

 

Aim:

We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus.  

Case details:

A 68-year-old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later. Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high-power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron-specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot-like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma.  

Conclusions:

Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.     

Type 1 protein tyrosine kinases in benign and malignant breast lesions

Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.  

Methods and results

Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.  

Conclusion

Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.     

Down-regulation of CD95 (Fas/Apo-1) in the epithelia of adenovirus-infected appendices

 

Aims:

Adenoviral inclusions are commonly seen in appendices from infants with intussusception. They are associated with focal epithelial budding and less frequently with epithelial shedding. These morphological changes could depend on the opposing effects of adenoviral gene products on CD95-mediated apoptosis.  

Methods and results:

Appendices from intussusceptions with viral inclusions ( n  = 4) and normal appendices ( n  = 10) were studied by immunochemistry with anti-adenovirus, anti-CD95 and anti-HLA-DR antibodies. Apoptosis was studied by the TUNEL method. The mucosa of normal appendices contained no adenoviral protein. CD95 was present in all epithelial cells except Paneth cells. HLA-DR was absent in epithelial cells and apoptosis was seen only in germinal centres and in a few surface epithelial cells. The epithelium of appendices from intussusceptions contained nuclear inclusions labelled with anti-adenovirus antibody, always found in the epithelial buds. The epithelial CD95 pattern was drastically altered in adenovirus-infected appendices. CD95 was absent from the budding foci. In these foci, HLA-DR was overexpressed. There was also increased epithelial apoptosis in areas remote from those lacking CD95 antigen.  

Conclusions:

The appearance of epithelial budding or shedding in appendices from intussusception could be due to focal in situ differences in the expression of adenoviral genes.     

乳腺导管内增生性病变及浸润性癌中树突状细胞的检测

目的　检测乳腺导管内增生性病变和微小浸润性癌及浸润性导管癌中树突状细胞(dendriticcells,DC)和T细胞的 分布状况和浸润密度,探讨乳腺癌发生、发展中机体免疫状态的变化规律。方法　应用免疫组化S P法和两步法对16例正常 副乳腺、58例导管内增生性病变、4例微浸润导管癌及67例浸润性导管癌乳腺标本进行S 100蛋白+DC、HLA DR+DC、CD1a +DC(DC三参数)及CD45RO+T细胞的浸润密度检测。结果　浸润癌中DC三参数浸润密度均高于其它病变组织(P< 0.05)。导管原位癌、微浸润癌及浸润癌组织中CD45RO+T细胞浸润密度均高于其它病变组织(P<0.05)。DC三参数间及 其与CD45RO+T细胞间均呈正相关(P<0.001)。结论　DC浸润密度随增生性病变加重而逐渐增高,发展为浸润癌时则明 显增高。     

HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry

AIM: To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC. METHODS AND RESULTS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed to detect HER2 in 270 IDCs with an intraductal component and in 50 pure DCIS samples; IHC was also performed in 116 metastatic nodes. HER2 was found to be amplified in 77 cases (28.5%) and overexpressed in 79 (29.3%) of the 270 IDCs. HER2 amplification was similar between intraductal and invasive components of the same tumour. The concordance for HER2 status between invasive and intraductal components of individual tumours was 98.5% and 99.3% by FISH and IHC, respectively. HER2 was amplified in 25 (50%) of the 50 pure DCIS samples. HER2 overexpression in metastatic nodes resembled the HER2 status in the primary tumour for 108 (93.1%) of 116 cases (kappa =0.831). CONCLUSION: Our study indicates that the intraductal component of IDC may differ biologically when compared with pure DCIS. HER2 appears to lack a critical role in the progression from DCIS to IDC and HER2 status is maintained in metastatic lesions.     

Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression

Aims : To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas (NHL).  

Methods and results

Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death ( n  = 33) or for an average of 63 months ( n  = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response.  

Conclusions

Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.     

Thyroid carcinoma associated with familial adenomatous polyposis

 

Aims:

Thyroid carcinoma is an extracolonic manifestation that is present in about 1% to 2% of patients with familial adenomatous polyposis (FAP). Less than 100 cases have been reported in detail. We have investigated the suggestion that FAP associated thyroid carcinoma is significantly different morphologically from both papillary and follicular types and can be considered as a separate entity.  

Methods and results:

Specimens from three patients with FAP associated thyroid tumours, all but one having single nodules, have been analysed. All three patients belonged to an extended kindred (23 siblings in four generations) who had genetic analysis and intensive screening for thyroid nodules. Seven patients had the same APC mutation at codon 1061. Pathological examination revealed a typical papillary carcinoma, encapsulated variant, in all patients, with follicular areas in one case. All thyroid specimens, in addition to histological and immunohistological examinations, were also specifically studied for activation of the RET-PTC oncogene, that seems to be restricted to papillary thyroid carcinoma. Two of the three patients had RET-PTC activation (PTC₁ isoform).  

Conclusions:

The findings suggest that the tumours were certainly papillary, at least in the present kindred. Further studies in different families are required for a better understanding of this peculiar tumour and of its biological behaviour.     

Mammary epidermoid inclusion cysts after wide-core needle biopsies

 

Aims:

To investigate the prevalence of squamous epidermoid inclusion cysts after wide-core needle biopsy.  

Methods and results:

Epidermoid inclusion cysts were found in five of 17 surgical excisions (29%) after preliminary wide-core needle biopsies in a 7-month period. Thereafter they were not seen in 26 subsequent postwide-core surgical excisions in a period of 6 months.  

Conclusions:

The cysts appear to be an iatrogenic complication of wide-core biopsy, and need morphological recognition in order to avoid confusion with spontaneous squamous metaplasia of benign or malignant breast epithelium. Longer term implications are unknown.     

Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser: correlation with histological grade and metastatic behaviour

 

Aims:

The purpose of this study is to examine the relationship between immunohistochemical localization of cathepsin D (CD), proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGF-R) in 65 cases of breast carcinoma in Japanese women and traditional prognostic factors such as histological grade, lymph node status, mitotic rate and clinical stage, in order to possibly identify some indicator(s) that may be specifically associated with prognosis.  

Methods and results:

Serial sections of 5-μm thick were cut from the archival formalin-fixed, paraffin-embedded tissue blocks, and processed for CD, PCNA and EGF-R immunostaining. The results were analysed by computer-based image analysis system. All samples showed a positive immunoreaction for cathepsin D in both the parenchyma and stroma. However, the staining area and intensity varied from cell to cell in the parenchyma and stroma as well as among samples. Subsequently, the evaluation of immunostaining for CD was separately performed in both the parenchyma and stroma (CDpar and CDstr, respectively) and the combination of both components (CDtotal). PCNA and EGF-R showed positive immunostaining almost exclusively in the parenchymal component of the carcinoma tissue specimens. CDtotal significantly correlated with the histological grade, PCNA index (PI), mitotic rate (MR), EGF-R and lymph node metastasis. Significant correlation was also demonstrated between CDpar and the histological grade, EGF-R and lymph node metastasis, or between CDstr and MR, EGF-R and lymph node metastasis. EGF-R correlated highly with the histological grade, MR score, lymph node metastases and recurrence-free survival.  

Conclusions:

Both the CD parameters and EGF-R are valuable indicators for predicting the biological behaviour of human breast carcinoma.     

CD109 expression in basal-like breast carcinoma

Breast cancer can be classified into several subtypes based on gene expression profiling. Basal-like breast carcinoma (BLC) has a triple negative phenotype, that is, the subtype lacks the estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). It has been recently reported that CD109, a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, is a new breast myoepithelial marker. In the present study CD109 expression was investigated in invasive ductal carcinomas (IDC) of the breast on immunohistochemistry. Eighty-eight formalin-fixed, paraffin-embedded breast carcinoma sections were immunostained with anti-CD109, anti-cytokeratin 5/6 (CK5/6), anti-calponin, anti-vimentin and anti-p63 antibodies. CD109 expression was detected in 18 of 30 basal-like breast carcinomas (BLC) but not in other types of 53 IDC (non-BLC) that were positive for ER, PgR and/or HER2. The percentage of CD109-positive tissues (60%) in BLC was similar to that of CK5/6 (63%) and higher than that of other myoepithelial markers including p63 (23%), calponin (33%) and vimentin (33%). Statistical analysis indicated that the CD109-positive group in BLC, but not the CK5/6-positive group in BLC, was associated with reduced fat invasion ( P  < 0.05). These findings indicate that CD109 is a useful diagnostic marker for BLC and that CD109 expression may affect biological properties of cancer cells.     

p34cdc2 in invasive breast cancer: relationship to DNA content, Ki67 index and c-erbB-2 expression

Aims : One-hundred and eighty-eight cases of human mammary carcinoma were examined immunohistochemically for their expression of Ki67, p34^cdc2 and c-erbB-2. DNA image cytometry was performed to evaluate DNA ploidy, Auer type, S-phase fraction (SPF), 5c exceeding rate (5cER) and 2c deviation index (2cDI).  

Methods and results

One-hundred and sixty-eight cases were invasive ductal carcinomas, 20 were of invasive lobular type. Routinely assessed oestrogen and progesterone receptor scores were available. The results were analysed statistically in comparison to tumour type, histopathological grade, lymph node status, menopausal status, patient age and overall survival. Ki67 ( P  < 0.002) and c-erbB-2 ( P  < 0.0001) correlated well with overall survival ( P  < 0.0008) and grade ( P  < 0.038) but not with lymph node status and tumour type. p34^cdc2 showed a trend towards a positive correlation with Ki67 ( P  < 0.058) and a significant negative correlation with receptor status ( P  < 0.008) but with none of the other parameters examined.  

Conclusions

No association between the DNA measured parameters (Auer type, SPF, 5cER and 2cDI) and survival was found. Our results suggest that c-erbB-2 and Ki67 are parameters which might, in combination with receptor status, help to define subgroups with different outcomes.