Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours

Expression of pS2 was studied by immunocytochemistry in normal breast tissue ( n = 20), benign tumours ( n = 9) and 145 breast cancers representative of the different histological types. pS2 immunostaining was scored as negative (D1 = 0-5% stained cells), positive (D2 = 5-75% stained cells) or highly positive (D3 > 75% stained cells). pS2 protein was evident in all normal breast samples examined. Six of nine benign lesions showed pS2 staining. In both cases, immunostaining was weaker than in breast cancers. Of breast cancers, 77/145 (53.1%) were pS2 positive, including 33.1% with intense staining. The presence of pS2 was not correlated with the age of patients, the size of the primary tumour, or lymph node status, but was correlated with histological grading and nuclear grading. pS2 expression was also correlated with menopausal status and oestrogen receptor status (59% of receptor-positive tumours were pS2 positive), but not to progesterone receptor status. pS2 expression in breast carcinomas is not a characteristic of specific histological types. Although this protein is predominantly expressed in oestrogen receptor-positive and differentiated tumours, it shows oestrogen-independent expression in about 30% of cases.     

Localization of p53 and proliferating cell nuclear antigen in fine-needle aspirates of benign and primary malignant tumors of the human breast: An immunocytochemical study using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method

p53 and proliferating cell nuclear antigen (PCNA) status was determined in fine-needle aspirates (FNAs) and methacarn-fixed paraffin-embedded tissue sections of six fibroadenomas and 50 primary breast carcinomas using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method. Nuclear accumulation of p53 was identified in 28% of carcinomas, while a heterogeneous immunostaining for PCNA was seen in all benign and malignant tumors examined. p53 expression in relation to nuclear pleomorphism and lymph-node status showed weak correlation only as to nuclear grade (r=0.28; P < 0.01). No direct or inverse correlation was found to exist between PCNA score and the evaluated prognostic parameters. In conclusion, although the identification of p53 in FNAs of breast tumors may assist in the diagnosis of malignancy, its application in the laboratory practice of cytopathology appears to be limited, since only 28% of primary breast carcinomas accumulate p53. Moreover, PCNA immunocytochemistry can be used as an alternative to traditional methods of evaluating the proliferative rate of tumors in FNAs. Diagn Cytopathol 1996;15:277–281. © 1996 Wiley-Liss, Inc.     

Elevated levels of p27, p21 and cyclin D1 correlate with positive oestrogen and progesterone receptor status in node-negative breast carcinoma patients

The search for better prognostic indicators and new treatment modalities in node-negative breast carcinoma patients is important. The aim of this study was to determine the immunohistochemical expression of central cell regulator proteins in relation to hormone receptor status, tumour-cell differentiation and prognosis. We investigated the immunoreactivity of p27, p21, cdk4, cyclin D1 and p53 in 77 node-negative breast carcinomas, with long-term follow-up (mean 163 months; range 20−227). Nuclear staining for p27 was seen in 87% of the carcinomas, for cdk4 in 92%, for p21 in 68%, for cyclin D1 in 58% and for p53 in 18%. Oestrogen receptor (ER) and progesterone receptor (PgR) nuclear staining was seen in 69% and 65% of the tumours, respectively. No correlation between the levels of p21 and p53 was observed. P21 overexpression was, however, associated with positive ER status. Elevated levels of p27 and cyclin D1 correlated with positive hormone status (both ER and PgR). We did find a significant correlation between p27 and cyclin D1 and histological grade of the tumours, with extensive positive immunostaining of p27 and cyclin D1 in well-differentiated carcinomas. The only significant prognostic factor in our series was histological grading. Ten-year relapse-free survival was significantly prolonged in patients with histological grade I tumours versus histological grade II and III tumours. Our results suggest that the expression of p27 and cyclin D1 is closely linked to hormone receptor status in breast carcinomas and to tumour differentiation, a finding that may be of importance in the treatment of hormone-dependent tumours. Received: 26 March 1998 / Accepted: 29 April 1999     

Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours

Gap junctional intercellular communication (GJIC) has been proposed as a cellular mechanism for tumour suppression and there is experimental evidence in support of this. If aberrant GJIC contributes to the formation of human breast tumours, one might expect that the connexins (gap junction proteins) expressed by epithelial cells in normal human breast would be down-regulated in tumour epithelial cells, or that tumour cells might show aberrant expression of other connexin family members. This study examines the immunocytochemical expression of connexins 26 (Cx26) and 43 (Cx43) in normal human breast, 11 benign breast lesions, two special-type carcinomas, and 27 invasive carcinomas of no special histological type (NST). Cx26 generally was not expressed at detectable levels in normal human breast, but punctate Cx43 immunostaining of the myoepithelial cells was found. Cx43 staining of the myoepithelium was also a feature of the benign lesions and ductal carcinoma in situ (DCIS). In general, the epithelial cells of benign lesions failed to stain for either connexin. Similarly, a lobular carcinoma did not express Cx26 or Cx43, but there was punctate Cx43 in the epithelial cells of a mucoid carcinoma. Cx26 was up-regulated in the carcinoma cells of 15 of the 27 invasive NST carcinomas, although the staining was usually cytoplasmic and heterogeneous. Cx43 was expressed by stromal cells, possibly myofibroblasts, in all NST carcinomas. Furthermore, there was heterogeneous Cx43 expression in the carcinoma cells of 14 of the 27 NST carcinomas and the staining was often intercellular and punctate, characteristic of functional connexins. Up-regulation of Cx26 and/or Cx43 in the carcinoma cells of over two-thirds of invasive lesions of NST is not necessarily inconsistent with a tumour suppressor role for GJIC. However, the role of gap junctions in the formation and progression of solid human tumours is likely to be more complex than indicated from experimental systems. © 1998 John Wiley & Sons, Ltd.     

p27/kip1 expression in normal epithelium, benign and neoplastic breast lesions.

The development of cancer in the breast and in other sites is a complex process requiring a number of different genetic and epigenetic alterations. The accumulation of the genetic changes is thought to underlie the progression from precancerous lesions to carcinomas. The expression of p27/kip1 protein, a cyclin-dependent kinase inhibitor, was investigated by immunohistochemistry in normal epithelial specimens, benign alterations, and malignant lesions of the breast. The number of p27/kip1-positive cells ranged from none to more than 98% in the overall series. Wide ranges of p27/kip1-positive cells were consistently observed within each histological category, but the median value progressively decreased in typical hyperplasia and fibroadenoma, with an even more marked reduction in malignant lesions, compared with normal epithelium. Moreover, the percentage of cells expressing p27/kip1 in tumours was about three times lower in invasive than in in situ lesions and was inversely related to tumour size, but not to lymph node involvement. In conclusion, the degree to which p27 expression is altered in typical hyperplastic lesions and fibroadenomas indicates that the deregulation of p27 may occur very early on during breast cell transformation, but the usefulness of its determination to categorize subgroups of lesions at different risk of evolution remains somewhat doubtful.     

Loss of laminin-5 in the epithelium-stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast

AIMS: To demonstrate immunohistochemically the alpha3 and gamma2 chain of laminin-5 in benign epithelial and malignant lesions of the human breast. METHODS AND RESULTS: The alpha3 chain was identified by the monoclonal antibody BM165 and the gamma2 chain by GB3 in shock frozen samples using APAAP (alkaline phosphatase monoclonal anti-alkaline phosphatase) technique. The pre-existing breast epithelium, the 12 benign ductal and lobular proliferations and the three fibroadenomas showed a continuous immunostaining in the basement membrane region. In contrast to benign epithelial lesions, the 44 cases of invasive breast carcinoma showed a loss of the laminin-5 chains in more than 50% of the carcinoma stroma interface. Twenty-four out of the 44 invasive carcinomas revealed a complete loss of laminin-5 immunostaining. Focal defects of the laminin-5 immunostaining were also found in ductal carcinoma in situ in its pure form. CONCLUSIONS: As recently described, the malignant transformation of breast epithelium with expression of an invasive phenotype is associated with a decrease of hemidesmosomes. The reduced immunostaining of laminin-5 is in line with this finding because laminin-5 represents the major component of the anchoring filaments attaching hemidesmosomes to the basement membrane. We feel that immunohistochemical demonstration of laminin-5 may serve as a marker of benignity in epithelial breast lesions. While other carcinoma types exhibit an increased laminin-5 deposition, which has been suggested as an invasion promoting factor, the loss of laminin-5 in breast cancer supports the view that breast carcinomas do not utilize laminin-5 for invasion.     

Histologic grading of noninvasive papillary urothelial tumors: validation of the 1998 WHO/ISUP system by immunophenotyping and follow-up

Cytokeratin (CK) 20, Ki-67, and p53 were applied to 84 noninvasive papillary urothelial tumors graded by the 1973 World Health Organization (WHO) and 1998 WHO/International Society of Urological Pathology (ISUP) systems. In the WHO/ISUP classification, all benign lesions showed normal CK20 staining and all carcinomas showed abnormal staining. The Ki-67 index was significantly different between benign and malignant lesions (P < .05) and between low- and high-grade carcinomas (P < .001). p53 was negative in all benign lesions, with a significant difference between low- and high-grade carcinomas (P < .001). Tumor recurrence was significantly different between low- and high-grade carcinomas (no recurrences among the papillary urothelial neoplasms of low malignant potential). By the 1973 WHO classification, normal CK20 staining was present both in benign lesions and in carcinomas. Ki-67 staining did not distinguish between grade 2 and grade 3 carcinomas (P > .05), and there was no difference in p53 staining in grades 1 and 2 carcinomas (P > .05). Recurrences were not different between grades 1, 2, and 3 carcinomas. All biologic markers studied and tumor recurrences were significantly different among papillary lesions classified by the WHO/ISUP system but not by the 1973 WHO system, validating the predictive value of the WHO/ISUP system and providing objective markers for the grading of papillary urothelial tumors.     

Typing and grading breast carcinoma on fine-needle aspiration: Is this clinically useful information?

The ability of fine-needle aspiration (FNA) to diagnose breast cancer is beyond question. The established role of cytopathology is to maintain a low benign to malignant biopsy ratio by reducing the number of benign lesions excised. Both typing and grading of breast cancers on FNA have received attention in the cytology literature but how this knowledge can influence management has not been fully explored. Recently we described a method for the cytological grading of breast cancer that compares well with the established Bloom and Richardson grades. In this paper we present our experience of 1,387 breast cancer FNAs reported by us with histological verification. We show that cytologically typing and grading breast cancers are valid exercises that can predict the true nature of the neoplasm. This information may assist in the clinical approach to the malignant breast. © 1995 Wiley-Liss, Inc.     

Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast

AIMS: This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues. METHODS AND RESULTS: Six hundred and ninety-nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre-treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6. CONCLUSIONS: Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in-situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.     

DIFFERENT PATTERNS OF HLA-DR ANTIGEN EXPRESSION IN NORMAL EPITHELIUM,HYPERPLASTIC AND NEOPLASTIC MALIGNANT LESIONS OF THE BREAST

Fifteen samples of non-tumoural breast tissue, 24 cases of benign lesions, four biopsies of inflammatory carcinomas and 94 tumour samples of primitive mammary carcinomas were analysed for HLA class II expression. We found, first, that HLA class II antigens were detectable in all cases of non-neoplastic breast tissue. Secondly, HLA class II antigen expression was notably increased in benign neoplasms and hyperplastic lesions. In contrast, only 32 out of 94 carcinomas showed expression of HLA-DR antigens, 17 tumours had HLA-DP antigens and 11 carcinomas were positive for the presence of DQ molecules. The expression of class II antigen was associated with the degree of histological differentiation (P < 0.05) but was independent of stromal leucocytic infiltration. Thirdly, HLA-DR was very strongly expressed in intravascular tumoural thrombi, especially in the ‘inflammatory carcinomas’. The immunephenotype of inflammatory infiltrate was analysed in benign and malignant lesions. In malignant lesions the mean number of inflammatory cells was significantly higher than in benign lesions. Interestingly, we found no differences in the amount and composition of inflammatory infiltrate between HLA-DR positive and negative tumours.     

A comparative analysis of core needle biopsy and fine-needle aspiration cytology in the evaluation of palpable and mammographically detected suspicious breast lesions

The present study was undertaken to compare the efficacy of needle core biopsy (NCB) of the breast with fine-needle aspiration cytology (FNAC) in breast lesions (palpable and non-palpable) in the Indian set-up, along with the assessment of tumor grading with both the techniques. Fifty patients with suspicious breast lesions were subjected to simultaneous FNAC and ultrasound-guided NCB following an initial mammographic evaluation. Cases were categorized into benign, benign with atypia, suspicious and malignant groups. In cases of infiltrating duct carcinomas, grading was performed on cytological smears as well as on NCB specimens. Both the techniques were compared, and findings were correlated with radiological and excision findings. Out of 50 cases, 18 were found to be benign and 32 malignant on final pathological diagnosis. Maximum number of patients with benign diagnosis was in the fourth decade (42.11%) and malignant diagnosis in the fourth as well as fifth decade (35.48% each). Sensitivity and specificity of mammography for the diagnosis of malignancy was 84.37% and 83.33%, respectively. Sensitivity and specificity of FNAC for malignant diagnosis was 78.15% and 94.44%, respectively, and of NCB was 96.5% and 100%, respectively. But NCB had a slightly higher specimen inadequacy rate (8%). NCB improved diagnostic categorization over FNAC by 18%. Tumor grading in cases of IDC showed high concordance rate between NCB and subsequent excision biopsy (94.44%) but low concordance rate between NCB and FNAC (59.1%). NCB is superior to FNAC in the diagnosis of breast lesions in terms of sensitivity, specificity, correct histological categorization of the lesions as well as tumor grading.     

Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: its correlation to histologic findings in 43 cases.

We examined Ki-67, p53, p21, and p27 immunolocalization in 43 cases of apocrine lesions of the breast and correlated these findings with histologic parameters to understand their biologic significance. Twenty cases were benign, 1 case was borderline, and 22 cases were diagnosed as malignant, including 9 intraductal and 13 invasive apocrine carcinomas. Both the ratio of Ki-67-positive cases (17 of 21 [88.9%] versus 1 of 19 [5.3%]; P < .001) and the Ki-67 labeling index of positive cases examined (15.0% versus 2.7%; P < .005) were significantly higher in malignant than in benign apocrine lesions. None of the benign or borderline cases was immunohistochemically positive for p53, but 15 of 22 malignant cases (68.2%) demonstrated p53 (P < .001). In addition, the ratio of p53-positive cases was significantly higher in high nuclear grade cases (11 of 13 [84.6%]) than in intermediate nuclear grade cases (4 of 9 [44.4%]; P < .05). P53 immunoreactivity was also positively correlated with the nuclear grade of carcinoma cases examined in this study. Neither p21 nor p27 demonstrated any correlation with histologic parameters or findings of the apocrine lesions. Results of these studies suggest that Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions.     

Studies of c-jun oncogene expression in human breast using a new monoclonal antibody,NCL-DK4

A new monoclonal antibody to human c-jun oncoprotein, designated NCL-DK4, has been produced. NCL-DK4 has been proved to be highly effective for use on formalin-fixed, paraffin-embedded tissues, enabling the study of c-jun expression at a cellular level in both normal and neoplastic human tissues. The expression of c-jun oncogene has been examined in normal, benign, and malignant breast tissues, and c-jun-specific immunoreactivity in carcinomas has been related to histological type, tumour grade, c-erbB-2, oestrogen receptor, progesterone receptor, and epidermal growth factor receptor expression. Normal and benign breast tissues showed c-jun-specific immunostaining, which was weaker and in fewer cells compared with the c-jun immunoreactivity observed in breast carcinomas. No relationship was found between the degree of immunostaining and the extent of proliferative changes in benign breast tissues. Ninety per cent of all breast carcinomas studied showed c-jun-specific nuclear staining. There were no statistically significant differences in the intensity of c-jun immunoreactivity among grade I, II, and III infiltrating ductal carcinomas. There was no significant relationship between c-jun oncoprotein expression and c-erbB-2, oestrogen, progesterone, and epidermal growth factor receptor immunoreactivity.     

乳腺导管内乳头状肿瘤187例临床病理及免疫组织化学特征

目的 探讨乳腺导管内乳头状肿瘤(IDPN)的诊断方法和标准.方法 收集187例IDPN患者的临床和病理资料,结合目前认可的2003年WHO乳腺和女性生殖系统肿瘤病理学和遗传学分类标准、Page等和Tavassoli的诊断标准,对其形态学特点进行分析,并对其中53例行CD10、p63、CK14、CK5/6、CK7、乳珠蛋白-1(MGB1)及p53免疫组织化学EnVision法染色分析.结果 187例IDPN患者中导管内乳头状瘤(IDPMa) 128例,不典型导管内乳头状瘤(A-IDPMa) 16例,导管内乳头状癌(IDPCa) 43例.IDPN在形态学上表现为不同程度的上皮细胞和间质增生,以及继发病变等,这些使病灶呈现异常复杂的多样性.免疫组织化学肌上皮标记(CD10和p63)染色在IDPMa、A-IDPMa及IDPCa的表达依次减少,组间比较差异均有统计学意义(均P＜0.001).基底型角蛋白(CK5/6和CK14)染色显示良性病变的表达呈镶嵌状阳性表达,在A-IDPMa的不典型区和IDPCa中表达明显减少或缺如,两者相比差异有统计学意义(P＜0.001).腺腔上皮标志物CK7染色各组间比较差异无统计学意义(P=0.06).MGB1在IDPCa组染色明显减少(P值分别为0.002和0.007),p53染色各组均呈阴性.结论 IDPN是一组组织学改变复杂的疾病,应注意其诊断标准的掌握.肌上皮、基底型角蛋白和腺腔上皮标志物联合应用在该组复杂病变中有很好的诊断和鉴别诊断价值.     

乳腺浸润性导管癌中HPV18、HPV16感染的研究

目的 :了解乳腺浸润性导管癌中HPV18、HPV16的感染情况 ,分析其是否是乳腺癌发生的危险因素及与临床病理的相关性。方法 :根据HPV16、HPV18的DNA序列 ,合成相应特异的寡核苷酸片段 ,用加尾标记法制备地高辛标记探针 ,用原位杂交法检测 5 1例乳腺浸润性导管癌、10例相应正常乳腺上皮及 15例良性乳腺病变中HPV18、HPV16的感染 ,并分析其与患者发病年龄、肿块大小及淋巴结转移的相关性。结果 :浸润性导管癌中HPV18或 16的总阳性率达 70 6 % ,其中HPV18与HPV16的阳性率分别为 5 8 8%、4 5 1% ,均明显高于正常乳腺上皮的感染率 (30 0 %、10 0 % ;P <0 0 5 ) ;乳腺良性病变的HPV18、16阳性率分别是 6 0 0 %、6 0 % ,其中HPV18的阳性率亦显著高于正常乳腺上皮 (P <0 0 5 )。结论 :(1)HPV16和18可能是乳腺浸润性导管癌发生的致病因子 ,HPV18尚可能与乳腺良性病变的发生有关。 (2 )HPV的感染与患者年龄、肿块大小及淋巴结转移无相关性。     

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma

p21^WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II+III) (P-0·017) and poor tubule formation (P-0·002), and was significantly less frequent in lobular carcinomas (P-0·0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1^CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P<0·001 …). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation. © 1998 John Wiley & Sons, Ltd.     

Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis

Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.     

Accuracy of frozen section diagnoses of breast lesions after introduction of a national programme in mammographic screening

AIMS: By introducing mammography screening programmes, the size of the detected breast lesions became smaller and the histopathological interpretation problems greater. The study's aim was to analyse the risks and possible limitations of the frozen section method. METHODS AND RESULTS: Frozen section consultations of breast lesions (n=559) 2 years before and 6 years after launching a national mammographic screening programme in 1992 were evaluated in regard of the benign/malignant ratio, tumour size, preoperative frozen section results and final permanent section diagnoses. The breast frozen section examinations of 1990 compared with those from 1998 declined from 70.7% (299/423) to 62.2% (260/418) (P < 0.01), the benign/malignant ratio from 1.09 to 0.54 (P < 0.0001), the rate of the conclusive, correct frozen section diagnoses from 96.3% to 91.9% (P < 0.03). The sensitivity dropped from 92.3% to 87.6%, the negative predictive value from 95.7% to 88.3%, whereas the negative likelihood ratio rose from 0.08 to 0.12. The 'small' (< or = 10 mm) invasive breast carcinomas increased from 14.2% to 22.3% (P < 0.01) and the 'in situ' carcinomas from 2.1% to 6.6% (P < 0.05). CONCLUSIONS: The declining sizes of breast tumours (< or = 10 mm), especially from radiologically detected lesions and sometimes without a macroscopic correlate, create new limitations and changing indications in the histopathological interpretation. Considering the performance of new diagnostic methods (i.e. large core needle biopsies), frozen sections of surgical specimens should not be the primary diagnostic procedure for breast lesions and should be performed only after other preoperative methods have failed.     

Mucoepidermoid carcinoma of the breast

Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All patients were women ranging in age from 29 years to 80 years. As histological grading is one of the most important prognostic factors in breast invasive carcinomas, MEC was graded using the Auclair et al. [1] grading system specific for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely employed grading system in breast cancer. It was found that the two different grading systems appear to be interchangeable in assessing the grade of MEC of the breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate (G. 2) and one high grade (G. 3). The cases were studied with immunohistochemistry and were found to have the same keratin pattern shown by their salivary gland counterpart. It was found that there are more similarities than differences between MEC of the breast and of salivary glands.