Low PTEN expression is associated with worse overall survival in head and neck squamous cell carcinoma patients treated with chemotherapy and cetuximab.

BACKGROUND: Platinum-based chemotherapy associated with cetuximab is the first-line treatment for inoperable recurrence or metastatic head and neck squamous cell carcinoma (HNSCC). There is no established biomarker for cetuximab efficacy in HNSCC. The PI3K pathway is one of the most frequently altered pathways in HNSCC. Loss of phosphatase and tensin homolog (PTEN) expression occurs in up to 30 % of cases. METHODS: This was a retrospective analysis of data from 61 patients with inoperable recurrence or metastatic HNSCC treated with cetuximab. PTEN, epidermal growth factor receptor and p16 expression were analyzed by immunohistochemistry and tested for association with clinical outcomes. RESULTS: Median overall survival was 11.4 months and progression-free survival was 6.9 months. Low PTEN expression was present in 26.2 % of patients and identified patients with worse prognosis. p16 was positive in only 8.5 % of tumors. CONCLUSIONS: Low PTEN expression in patients treated with cetuximab plus chemotherapy emerged as a prognostic biomarker and should be evaluated for its predictive role for cetuximab efficacy.

Octreotide scintigraphy for the detection of paragangliomas.

Paragangliomas are neuroendocrine tumors located primarily in the head and neck region, but they can also occur at other sites. Confirming the preoperative diagnosis and detecting synchronous tumors may be difficult in some patients. Octreotide is a somatostatin analog that, when coupled to a radioisotope, produces a scintigraphic image of tumors expressing somatostatin type 2 receptors. Paragangliomas, like many neuroendocrine tumors, have been found to have a high density of somatostatin type 2 receptors on the cell surface. This study compared the results of preoperative octreotide scintigraphy with the histopathology in 21 patients who underwent surgery for presumed head and neck paragangliomas. Octreotide scan findings were positive in 16 patients with paragangliomas and negative in 3 patients with other pathology. One false-positive and 1 false-negative result were obtained. Thus, this test had an accuracy of 90%, a sensitivity of 94%, and a specificity of 75%. Previously unidentified synchronous tumors were identified in 5 patients. On the basis of this series of patients, octreotide scintigraphy appears to be a reliable test to detect paragangliomas and may be quite helpful in preoperative planning.

Distinction of basaloid squamous cell carcinoma from adenoid cystic and small cell undifferentiated carcinoma by immunohistochemistry.

Basaloid squamous cell carcinoma (BSCC) is a recently recognized variant of squamous cell carcinoma (SCC) with a predilection to occur in the tongue base, hypopharynx, and supraglottic larynx. In smal biopsy specimens, these tumors can be difficult to distinguish from small cell undifferentiated carcinoma (SCUC) and adenoid cystic carcinoma (ACC). Monoclonal antibodies reactive with cytokeratin (AE1/AE3, 34betaE12, Cam 5.2) as well as a variety of other cellular antigens (vimentin, actin, desmin, chromogranin, synaptophysin, CD57, neuron-specific enolase [NSE], and S100) were used in an immunoperoxidase method with paraffin-embedded tissue to phenotypically characterize 23 cases of BSCC, 10 cases of SCUC, and 15 cases of ACC. The neoplastic cells in 22 of the 23 cases of BSCC reacted with the high-molecular-weight cytokeratin antibody 34betaE12, whereas no reactivity was seen in any of the 10 cases of SCUC. This pattern of 34betaE12 reactivity more consistently differentiated BSCC from SCUC than did reactivity with the neuroendocrine markers chromogranin, synaptophysin, CD57, and NSE. These findings show that immunoperoxidase stains performed on paraffin-embedded tissue are potentially useful in establishing a diagnosis of basaloid squamous cell carcinoma.

p53 expression: a potential biomarker for risk of multiple primary malignancies in the upper aerodigestive tract.

The concept of field cancerisation assumes that in head and neck cancer patients (HNCP) with multiple malignancies the second primary cancers may arise independently from the entire upper aerodigestive tract as a consequence of massive exposure to common carcinogens. Since mutations and/or overexpression of the p53 tumour suppressor gene represent a genetic alteration frequently occurring in HNCP, we analysed immunocytochemically p53 oncoprotein expression in first primary, second primary cancers and in macroscopically uninvolved normal epithelium from different sites of the upper aerodigestive tract from 12 HNCP with multiple malignancies, in comparison with p53 expression in biopsy specimens of the upper aerodigestive tract from 5 non-neoplastic heavy smokers, as controls. In patients with multiple malignancies 6 cases (50%) showed positive staining of both first and second primaries, whereas 3 (25%) had positive labelling of first primary cancer but not of the subsequent second primary, 2 (17%) patients showed p53 expression only in the second primary cancer, and finally only 1 patient (8%) showed no p53 immunoreactivity in both first and second primary tumours. Moreover, 10 out of 12 (83%) HNCP with multiple cancers showed p53-positive staining in the normal epithelium from different sites of the upper aerodigestive tract, also at a significant distance from the site of first and second primary malignancies. contrast, sporadic p53 immunostaining was observed only in three out of 35 (8.5%) specimens from non-neoplastic controls. In addition, in 4 HNCP with multiple tumours the histological examination of apparently normal epithelium from the upper aerodigestive tract revealed signs of moderate or severe dysplasia, and in 1 case an in situ carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of quantitative DNA measurements and cytomorphology in squamous cell carcinomas of the upper aerodigestive tract with and without lymph node metastases.

Cytologic smears of squamous cell carcinomas (UICC T2 through T4) from the mucosa of the upper aerodigestive tract without cervical lymph node metastases (n = 10) and with metastases (n = 20) were examined. Subsequently, the cytologic smears of the metastases (n = 20) obtained by fine-needle aspiration or following neck dissection were evaluated morphologically. Each specimen was then stained with Papanicolaou and Feulgen techniques, and quantitative DNA measurements were performed with an image analysis system. Morphologically, the primary tumors with metastases revealed an increased mean nuclear perimeter and mean nuclear area compared with tumors unassociated with metastases. On quantitative DNA measurements, the tumors with metastases had an increased DNA content, a higher 2c deviation index, and a higher DNA malignancy grade and increased number of aneuploid cells. The specimens obtained from the metastatic nodes yielded the highest values for mean DNA content, 2c deviation index, aneuploidy, and malignancy grade. The stem lines of metastasis were always nondiploid. These data indicate a positive correlation between aneuploid tumor cell clones in primary cancer and the manifestation of lymph node metastases.

[A comparative study on proliferative activity in different histological patterns of adenoid cystic carcinoma--from a viewpoint of nuclear DNA contents].

Adenoid cystic carcinoma generally consists of the following histologic features: tubular, cribriform, trabecular, and solid. To investigate how these histological patterns affect the prognosis of this carcinoma, we determined the proliferative activity of each of the histologic patterns by cytofluorometry. Twenty-six cases of adenoid cystic carcinoma, obtained by surgical resection, were studied. According to predominant histological pattern, they were divided into three groups: seven cases were of cribriform pattern, nine cases of trabecular pattern, and ten cases of solid pattern. The region with each dominant pattern was obtained from biopsy specimen, and the nuclear DNA contents of the tumor cells of the regions were assayed. In four of twenty-six cases, that of the tumor cells of the region with other patterns in the same specimens were also assayed. The results were the following: 1) The mean incidence of over 4.5C-polyploid cells of the region with predominant pattern of each tumor significantly increased in the following order: cribriform pattern and solid pattern. 2) The incidence of over 4.5C-polyploid cells, in comparison of a predominant pattern with other histologic patterns in the same tumor, were calculated. It was higher in solid pattern than in trabecular pattern, and was higher in trabecular pattern than cribriform pattern. 3) Only two of ten cases, had aneuploidy in the region with predominant solid pattern and the other cases had diploid stem line. Judging from the above results, it was concluded that proliferative activity of each pattern increased in the following order: cribriform pattern, trabecular pattern, solid pattern.(ABSTRACT TRUNCATED AT 250 WORDS)