Cytogenetic analysis of sinonasal carcinomas.

BACKGROUND: Sinonasal carcinomas, including nonkeratinizing (NK) squamous cell carcinoma (SCC) and sinonasal undifferentiated carcinoma (SNUC), are uncommon malignant neoplasms arising from the Schneiderian respiratory epithelium of the nasal cavity and paranasal sinuses. Due to their low frequency, the cytogenetic data on these tumors is limited. METHODS: Seventeen patients who were operated on in our institution for extirpation of paranasal carcinomas were enrolled in this study. Fourteen pathologically confirmed samples of sinonasal carcinomas were cytogenetically analyzed using G-banding techniques after short-term culture. Three samples did not grow on culture. RESULTS: Five of the 14 sinonasal carcinomas had an abnormal karyotype (36%). Of the 9 NK SCCs, 3 had abnormal karyotypes with numerical and structural chromosomal anomalies. Of the 5 patients with SNUC, 2 had an abnormal karyotype. One case of SNUC had a diploid complex karyotype. Another case of SNUC had a near triploid composite karyotype with 60-69 chromosomes. The chromosome arms that involved frequent breakpoint and rearrangements were: 1p, 6p, 7p, and 12q. We found that 3 of the 3 patients who died of disease displayed an abnormal karyotype, whereas 2 of the 11 patients who are alive displayed an abnormal karyotype (P = 0.027). CONCLUSIONS: The study revealed that more than a third of the paranasal carcinomas carry an abnormal karyotype. No specific common aberrations were found in these tumors. To our knowledge this is the first attempt to investigate sinonasal squamous and undifferentiated carcinomas on a genetic level using G-banding technique. Additional studies are required in order to determine whether cytogenetic data may serve as an adjunct to conventional pathology for the diagnosis and prognosis assessment of these rare and highly aggressive tumors.     

Expression of p16 in Sinonasal Undifferentiated Carcinoma (SNUC) Without Associated Human Papillomavirus (HPV)

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon and highly aggressive neoplasm of the paranasal sinuses and nasal cavity. Its undifferentiated histologic appearance often requires immunohistochemical studies to distinguish it from other high-grade neoplasms. Due to the rarity of SNUC, its immunohistochemical staining profile has been incompletely characterized, and little work has been done on its expression of the markers for human papillomavirus (HPV). Our objective is to expand our knowledge of its immunophenotype and its association with HPV in order to define markers with mechanistic potential in the disease process, or of possible therapeutic importance. A total of five patients (one woman and four men) with SNUC, ranging in age from 26 to 75 years (mean 56.8 years) were compared to five patients (five men) with poorly differentiated squamous cell carcinoma (PDSCC), ranging in age from 53 to 75 years (mean 62.2 years). PDSCC was chosen as a control, given its well-reported immunohistochemical profile and negativity for HPV markers. The immunohistochemical panel included: CK7, CK19, EMA, NSE, chromogranin, p53, CK5/6, p63, CK14, S100, HMB-45, desmin, muscle specific actin, and CD45. Additionally, tests for p16, EBV, and HPV (subtypes 6, 11 16, 18) were performed. The diagnosis of SNUC was confirmed in all cases by histology and immunohistochemical stains. An interesting finding of strong diffuse positivity for p16 was noted in all SNUC cases, compared to only two of five PDSCC that were positive for p16. HPV DNA was not detected in any SNUC cases or any cases of PDSCC. All SNUC cases demonstrated over expression of p16 in the absence of HPV DNA expression. This may represent residual epithelial p16 staining, which is normally present in the sinonasal tract. Due to the rarity of SNUC, more cases will need to be evaluated to confirm the absence of HPV DNA.     

Cyclin D1 expression in oral squamous cell carcinoma and verrucous carcinoma: correlation with histological differentiation.

OBJECTIVE: To assess the expression of cyclin D1 in oral squamous cell carcinoma (OSCC) and verrucous carcinoma (VC), to compare its expression in both of these carcinomas, and to investigate the possible correlation of cyclin D1 expression in different histological grades of OSCC. STUDY DESIGN: Paraffin embedded tissues from 71 cases of OSCC and VC were studied immunohistochemically. Expression of protein was correlated between the 2 entities and in different grades of OSCC. RESULTS: Cyclin D1 overexpression was seen in 29 cases (70.7%) of OSCC and in 19 cases (63.3%) of verrucous carcinoma. Statistical significance at the 5% level was observed for cyclin D1 expression between all categories of squamous cell carcinoma (SCC), that is, between well-differentiated and moderately differentiated carcinomas, and between moderate and poorly differentiated carcinomas, and well and poorly differentiated squamous carcinomas. No statistical significance was observed in cyclin D1 expression between SCC and oral verrucous carcinoma; however, statistical significance was seen between oral VC and poorly differentiated squamous cell carcinoma. CONCLUSION: Increased expression of cyclin D1 significantly correlated with lack of differentiation in these malignant epithelial neoplasms.     

Sinonasal undifferentiated carcinoma: immunohistochemical profile and lack of EBV association

The role of Epstein-Barr virus (EBV) in the development of sinonasal undifferentiated carcinoma (SNUC) remains unresolved. Reports of EBV-positivity in SNUC may reflect inclusion of lymphoepithelioma-like carcinomas within this group. In addition, SNUC have been incompletely characterized immunohistochemically, and their undifferentiated appearance often requires such ancillary studies to aid in their distinction from other high-grade neoplasms. To address these two issues, 25 cases of SNUC diagnosed between the years 1983 and 1999 were selected from our files. EBER in situ hybridization (ISH) was performed on the paraffin-embedded tissue by using 3H-labeled EBER-1 RNA probes. Neoplasms with sufficient tissue (22 of 25) were evaluated immunohistochemically for Ki-67, p53, chromogranin, synaptophysin, placental alkaline phosphatase (PLAP), CD99, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), neuron-specific enolase (NSE), and latent membrane protein-1 (LMP-1). The median patient age was 58 years (range, 20-81 years), with a male-to-female ratio of approximately 3:1. The most common tumor location was the nasal cavity (18 cases), followed by the ethmoid and maxillary sinuses. Median survival was 18 months. All 25 tumors were negative for EBER-I by ISH. Ki-67 was negative in one case, 1+ in nine, 2+ in six, 3+ in five, and 4+ in one. P53 was negative in nine, 1+ in five, 2+ in two, 3+ in none, and 4+ in six. CD99 expression was strongly positive in 3 of 22 (14%) and completely negative in the remainder. Variably intense focal staining for EMA was present in 4 of 22 (18%). NSE faintly stained 4 of 22 (18%). Chromogranin, synaptophysin, PLAP, CEA, and LMP-1 were negative (0 of 22). Our results suggest that EBV does not play a role in the development of SNUC. Strict histologic criteria are necessary to avoid confusion with lymphoepithelioma-like carcinoma or other high-grade malignancies in this region. The finding of occasional CD99-positive cases adds SNUC to the growing list of CD99-positive neoplasms.     

Cytokeratin 20, AN43, PGDH,and COX-2 expression in transitional and squamous cell carcinoma of the bladder

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage.     

Utility of p40 in the Differential Diagnosis of Small Round Blue Cell Tumors of the Sinonasal Tract

The sinonasal tract may give rise to a broad range of neoplasms that share a “small round blue cell” tumor (SBRCT) appearance on routine histology, but treatment strategies depend on precise tumor classification. Immunohistochemistry for p63 is often employed in the sinonasal SRBCT differential diagnosis because it is highly sensitive for squamous cell carcinoma (SCC). However, p63 staining may be observed in other tumor types, a potential diagnostic pitfall. P40 is a more squamous-specific isoform of p63, and it may be more useful in distinguishing poorly differentiated SCC from its mimickers in the sinonasal tract. Immunohistochemistry for p40 and p63 was performed on 171 sinonasal neoplasms with SRBCT morphology: 73 SCCs (67 poorly differentiated, non-keratinizing, or basaloid types and 6 nasopharyngeal carcinomas), 46 esthesioneuroblastomas, 11 sinonasal undifferentiated carcinomas (SNUCs), 11 lymphomas, 9 melanomas, 7 alveolar rhabdomyosarcomas, 4 solid adenoid cystic carcinomas, 4 NUT midline carcinomas, 4 primitive neuroectodermal tumors (PNETs), and 2 small cell carcinomas. P40 was positive in 72 of 73 SCCs, and showed a diffuse distribution in all but one positive case. P40 immunoexpression was also observed in 13 of 46 (28 %) esthesioneuroblastomas, 6 of 11 (55 %) SNUCs, 2 of 4 (50 %) adenoid cystic carcinomas, 3 of 4 (75 %) NUT midline carcinomas, 1 of 2 (50 %) small cell carcinomas, and 1 of 4 (25 %) PNETs; in the non-SCC tumors, p40 staining was focal in most cases. P63 was positive in every p40-positive tumor. In addition, a p63+/p40− phenotype was seen 5 of 11 (45 %) lymphomas, 4 of 7 (57 %) alveolar rhabdomyosarcomas, 1 of 4 (25 %) PNETs, and 3 of 46 (7 %) esthesioneuroblastomas. All sinonasal melanomas were negative for both markers. In the sinonasal SRBCT differential diagnosis, both p40 and p63 are highly sensitive for SCC, but p40 is more specific. Notably, p40 is consistently negative in lymphomas and alveolar rhabdomyosarcomas, two tumors that are frequently p63-positive. It must be remembered, however, that even diffuse p40 immunostaining is not entirely specific for the squamous phenotype, and therefore it should be utilized as part of an immunohistochemical panel.     

Sinonasal undifferentiated carcinoma and nasopharyngeal-type undifferentiated carcinoma: two clinically, biologically, and histopathologically distinct entities

Sinonasal undifferentiated carcinoma (SNUC) is a rare aggressive neoplasm arising in the nasal cavity and paranasal sinuses. Primary sinonasal nasopharyngeal-type undifferentiated carcinoma (PSNPC) is an even rarer tumor that has not been adequately reported. Both tumors have been reported to be associated with Epstein-Barr virus (EBV). We studied the clinicopathologic features and EBV status of 36 SNUC and 13 PSNPC patients from Taiwan, an EBV endemic area. The median age of SNUC patients was 53 years (range 20-76 years), with a male/female ratio of approximately 2:1. Five patients had histories of previous nasopharyngeal carcinoma treated with irradiation 6-26 years earlier. The most common locations were nasal cavity and ethmoid sinus. Orbital and intracranial invasion and distant metastasis were frequent findings. The median survival was 10 months. All 36 tumors were negative for EBER-1 by in situ hybridization. The median age of PSNPC patients was 58 years (range 36-75 years), with a male/female ratio of approximately 2:1. The most common location is nasal cavity. Eight patients achieved disease-free survival. Eight tumors had the morphology of lymphoepithelioma, whereas significant inflammatory infiltrate was not detected in the other five tumors. All 13 tumors were positive for EBER-1 by in situ hybridization. Because of the difference in the relation with EBV, prognosis, and response to radiotherapy, SNUC and PSNPC should be considered as two entirely different entities. The most important criteria for PSNPC are vesicular nuclei, syncytial pattern, spindle cells, and absence of necrosis.     

Among Sinonasal Tumors,CDX-2 Immunoexpression is not Restricted to Intestinal-Type Adenocarcinomas

Intestinal-type adenocarcinoma (ITAC) is a rare form of sinonasal cancer characterized by an association with exposure to industrial dusts, aggressive clinical behavior, and histologic/immunophenotypic similarity to tumors of the gastrointestinal tract. ITAC is sometimes very poorly differentiated and difficult to distinguish from other sinonasal neoplasms, particularly in a limited biopsy. CDX-2 and cytokeratin 20 are consistently immunoreactive in ITAC and as a result, these immunostains are often used to support the diagnosis. However, CDX-2 and cytokeratin 20 have not been tested on a broad range of sinonasal tumors, so their specificities remain unknown. Immunohistochemistry for CDX-2 and cytokeratin 20 was performed on 6 sinonasal ITACs as well as 176 non-intestinal-type sinonasal neoplasms. CDX-2 and cytokeratin 20 were positive in all 6 cases of ITAC. CDX-2 immunoexpression was also observed in 17 of 176 (10 %) non-intestinal-type tumors including 6 of 16 (38 %) sinonasal undifferentiated carcinomas, 8 of 81 (10 %) squamous cell carcinomas (including 5 of 39 non-keratinizing variants), 2 of 20 (10 %) salivary-type adenocarcinomas, and 1 of 2 (50 %) small cell carcinomas. In contrast, among non-intestinal types of sinonasal tumors, cytokeratin 20 was only focally observed in 1 of 176 non-intestinal tumors (a non-keratinizing squamous cell carcinoma). All cases of non-intestinal surface-derived adenocarcinoma and esthesioneuroblastoma were negative for both markers. Both CDX-2 and cytokeratin 20 are highly sensitive for the diagnosis of sinonasal ITAC, but cytokeratin 20 is more specific. CDX-2 staining may be observed in other high grade tumor types, especially sinonasal undifferentiated carcinoma and non-keratinizing squamous cell carcinoma. As a result, in the setting of a poorly differentiated sinonasal carcinoma the diagnosis of ITAC should not be based on CDX-2 immunoexpression alone. Clear-cut glandular differentiation and cytokeratin 20 immunoexpression are more reliable features.     

Prevalence of high-risk human papillomavirus DNA in nonkeratinizing (cylindrical cell) carcinoma of the sinonasal tract: a distinct clinicopathologic and molecular disease entity

Carcinomas of the nose and paranasal sinuses are a heterogeneous group of neoplasms that differ histologically, biologically, and clinically. Some of these tumors are known to harbor high-risk human papillomavirus (HPV) DNA. In an attempt to identify specific phenotypes associated with HPV infection, 39 cases of sinonasal carcinomas were evaluated by PCR for the presence of HPV DNA. The tumors were also studied with a panel of immunohistochemical stains, including p16, p53, and Ki-67 antibodies. Twenty-one cases were identified as keratinizing squamous cell carcinoma (KSCC) with a male-to-female ratio of 3:1. Eight cases were nonkeratinizing (cylindrical cell) carcinoma (NKCa) with a male-to-female ratio of 1:1. Ten cases were sinonasal undifferentiated carcinoma (SNUC), and 9 of these patients were men. HPV DNA, particularly type 16, was detected in 9 cases: 4 of 21 (19%) of KSCC, 4 of 8 (50%) of NKCa, and 1 of 10 (10%) of SNUC. In addition to a higher prevalence of HPV DNA in NKCa, the tumors also showed a distinct immunophenotype characterized by strong and diffuse staining for p16, high labeling scores for Ki-67, and negative or low reactivity to p53. On the other hand, KSCC and SNUC were either negative or weakly reactive to p16 antibodies. KSCC cases were more likely to be positive and more strongly reactive to p53 stain. Unlike KSCC, SNUC had high Ki-67 labeling scores. These observations suggest that NKCa of the sinonasal tract is a distinct histopathologic and molecular disease entity, which should be added to the list of upper aerodigestive tract tumors with strong etiologic relationship to high risk HPV.     

Expression pattern of apurinic/apyrimidinic endonuclease in sinonasal squamous cell carcinoma

Objective To evaluate the apurinic/apyrimidinic endonuclease 1 (APE1) expression in sinonasal squamous cell carcinomas (SCC) and to examine the correlation between APE1 expression patterns and various clinicopathological factors associated with sinonasal SCC that include SCC with inverted papilloma (SCCwIP) and SCC alone. Study Design Case-control study. Setting Chungnam National University Hospital. Subjects and Methods The expressions of APE1 were analyzed by means of immunohistochemistry in 30 sinonasal SCC, including 14 SCC patients associated with IP and 16 patients with SCC alone. A total of 19 patients who had been diagnosed with chronic rhinosinusitis with nasal polyposis and who required endoscopic sinus surgery were used as the control group. The degrees of APE1 expression were analyzed with respect to the following clinicopathologic variables: age, sex, T stage, histologic differentiation, distant metastasis, and recurrence. Results Cytoplasmic staining of APE1 was significantly higher in SCC compared with SCCwIP (68.75% vs 14.29%). Cytoplasmic staining of APE1 was significantly associated with T stage (P = .044) in SCC and histologic grade (P = .0025) in sinonasal SCC. Nuclear staining of APE1 was significantly associated with distant metastasis (P = .022) in SCC. Conclusion These results suggest that the nuclear and cytoplasmic expression of APE1 may be related to tumor invasiveness and prognosis in sinonasal SCC. The suppression of APE1 expression can potentially be a new target for future sinonasal SCC therapies.     

Management of sinonasal undifferentiated carcinoma

BACKGROUND: Our aim was to report the outcomes of treatment for sinonasal undifferentiated carcinoma (SNUC). METHODS: Between September 1992 and October 2005, 15 patients were treated with curative intent with surgery (n=1), surgery and adjuvant radiotherapy (n=9), and definitive radiotherapy (RT) (n=5). Follow-up ranged from 11 to 151 months (median, 30); follow-up on living patients ranged from 12 to 151 months (median, 22). No patient was lost to follow-up. RESULTS: Seven patients (47%) developed a recurrence from 3 to 50 months (median, 9) after treatment. The 3-year outcomes were: local control, 78%; locoregional control, 65%; distant metastasis-free survival, 82%; cause-specific survival, 77%, and survival, 67%. The local control rates versus treatment modality were: surgery, 0/1 (0%); surgery and postoperative RT, 7/7 (100%); preoperative RT and surgery, 2/2 (100%); and definitive RT, 2/5 (40%). One patient (7%) treated with surgery and postoperative RT sustained a fatal complication. CONCLUSIONS: Combined surgery and adjuvant RT likely offer the best chance of cure compared with either modality alone. The impact of adjuvant chemotherapy is unclear.     

Studies on biological characteristics of undifferentiated carcinoma of the esophagus]

To study the biological characteristics of undifferentiated carcinoma of the esophagus, the nuclear DNA content, the growth fraction using monoclonal antibody Ki-67 (Ki-67), immunohistochemical expression of epidermal growth factor receptor (EGFR) and the grade of Leu-7 positive cells infiltrating at the marginal area of the cancerous tissue were measured in 5 cases of undifferentiated carcinoma and 131 cases of squamous cell carcinoma. The following results were obtained. 1) DNA aneuploid was found in 60% of undifferentiated carcinoma, 47% of squamous cell carcinoma. 2) The Ki-67 labeling rates of undifferentiated carcinoma were higher than those of squamous cell carcinoma, and a variable proportion of Ki-67 labeling rates of undifferentiated carcinoma was ranging from 12% to 34%. It was demonstrated that undifferentiated carcinoma had high proliferative potential. 3) The expression of the EGFR was stained in the basal cell and parabasal layers of normal epithelia. In squamous cell carcinoma, EGFR was located on the cancer cell membrane and was observed 79%, while in all cases of undifferentiated carcinoma, it was not detected. 4) The grade of Leu-7 positive cells was related to pathological stage and prognosis in squamous cell carcinoma. The patients with low grade of Leu-7 positive cells frequently had early recurrences of the carcinoma after esophagectomy, and their prognosis was poorer than those with higher grade of Leu-7 positive cells. The patients of undifferentiated carcinoma, independently of pathological stage, were observed low grade of Leu-7 positive cells and had poor prognosis except only one case. Therefore undifferentiated carcinoma seems to be escaped from defensive mechanism of host immune response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathologic characteristics of NUT midline carcinoma arising in the mediastinum

NUT midline carcinomas (NMCs) comprise a group of highly aggressive tumors that have been reported primarily in the head, neck, and mediastinum of younger individuals. These tumors overexpress the nuclear protein in the testis (NUT), most commonly due to a chromosomal translocation that fuses the NUT gene on chromosome 15 with the BRD4 gene on chromosome 19. Although the earliest recognized cases were described in the thymus or mediastinum, an extensive survey for NMCs among malignant thymic or other mediastinal neoplasms has not been reported. We examined NUT expression in 114 cases of poorly differentiated carcinomas or unclassified mediastinal malignancies using a clinically validated NUT-specific monoclonal antibody. Four of 114 (3.5%) cases showed nuclear NUT expression. A NUT translocation was confirmed by fluorescence in situ hybridization in 3 of these cases. These tumors arose in 2 men and 2 women with a median age of 50 years (range, 28 to 68 y). Three of the tumors were originally diagnosed as undifferentiated epithelioid or round cell malignant neoplasms; 1 tumor contained focal squamous differentiation and was originally diagnosed as a poorly differentiated squamous carcinoma of probable thymic origin. We find that the incidence of NMC within the mediastinum, particularly among undifferentiated tumors, is similar to that reported at other anatomic sites. NMC should be considered in the differential diagnosis of any poorly differentiated epithelioid mediastinal tumor, regardless of age.     

Clinicopathologic study of thyroid carcinoma infiltrating the trachea

A clinicopathologic study of 14 cases of thyroid carcinoma with tracheal infiltration and 70 control cases of thyroid carcinoma without tracheal infiltration was performed. The cases with tracheal infiltration were classified into well differentiated carcinoma in 5 cases, poorly differentiated carcinoma in 6, undifferentiated in 2, and squamous cell carcinoma in one, thus showing a higher frequency (54.5%) of poorly differentiated carcinoma than that (11.4%) in the control cases. A comparative study of biological behavior between well differentiated and poorly differentiated carcinomas revealed that the latter was more aggressive, and the lymphnode metastatic rate of which was higher. The prognosis of poorly differentiated carcinoma was poorer than that of well differentiated carcinoma. Selective en bloc resection of the tumor including the larynx and trachea was followed by the improved prognosis of advanced thyroid carcinoma with tracheal infiltration.     

直肠癌全直肠系膜切除术系膜切缘微转移的临床研究

目的 对直肠癌患者系膜切缘微转移灶进行检测,研究其对局部复发的影响.方法 对52例Dukes A、B和C期直肠癌患者实施伞直肠系膜切除术,用RT-PCR技术检测系膜切缘组织细胞中角质蛋白CK20 mRNA.结果 本组52例直肠癌旁系膜中,21例CK20 mRNA呈阳性,31例为阴性,总阳性率为40%.Dukes A、B和C期阳性率分别为17%、30%和54%,直肠系膜切缘微转移发生率随肿瘤分期升高而增加,组间比较差异有统计学意义,P<0.05;高、中、低与未分化癌阳性表达率分别为43%、38%、40%和50%,病理分级之间CK20 mRNA表达阳性率差异无统计学意义(P>0.05).全组患者局部复发率为12%,CK20 mRNA阳性组和阴性组局部复发率分别为24%和3%,两组比较差异有统计学意义,P<0.05.结论 直肠系膜切缘微转移与局部复发有关,提示系膜CK20mRNA可能是一个潜在的局部复发标志物.     

Metaplastic breast carcinomas: are they of myoepithelial differentiation?: immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers

We investigated 20 spindle cell (sarcomatoid) metaplastic carcinomas (MCs) without squamous differentiation. In addition, five high-grade phyllodes tumors were assessed for comparison. Our immunohistochemical antibody panel included pan-cytokeratin (CK), low molecular weight CK (CK8/18), four basal cell type CKs (34betaE12, CK5/6, CK14, and CK17), vimentin antibodies, as well as antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers. Sixteen of the 20 tumors (80%) expressed at least two markers of the combination CD10/p63/SMA. S-100 detected 1 case negative for CD10/p63/SMA and 3 cases that only expressed one marker of this combination. While 18 MCs (90%) were positive for CD29, 14-3-3sigma (11 cases) and maspin (9 cases) were observed in 55% and 45%, respectively. Antibodies to pan-CK and the basal cell type CKs were strongly reactive in 12 tumors (60%), but in 6 cases (30%) positivity for these markers was weak and only focal; 2 MCs showed no positivity for CK. The stromal component of all phyllodes tumors was positive for vimentin, whereas all other investigated markers were absent except for focal p63 and CD10 expression in 1 case each. Our findings convincingly show a myoepithelial immunophenotype in sarcomatoid MCs, which is demonstrated by the presence of basal cell type CKs and the combination of the established myoepithelial markers CD10, p63, SMA, and S-100. We conclude that tumors with weak or even absent CK expression should only be diagnosed as primary sarcomas of the breast after exclusion of a myoepithelial immunophenotype. CD29 and 14-3-3sigma represent valuable novel myoepithelial markers in these diagnostically difficult cases.