PMC3568520_01
Upper endoscopy showing a friable, ulcerative esophageal tumor in Barrett's esophagus (BE) in case A. Islets of squamous epithelium were seen within the BE mucosa.
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F1
Mutation analysis of the TP53 gene showed a point mutation in exon 5 (H179N) in the ESCC and a deletion of 14 nucleotides in exon 6 (c.622_635delGACAGAAA CACTTT, p.D208SfsX3) in the HNSCC (Fig. 4D, Table 1), the latter being consistent with abrogated nonfunctional p53 protein.
PMC3568520_02
Upper endoscopy showing a friable, ulcerative esophageal tumor in Barrett's esophagus (BE) in case A. Islets of squamous epithelium were seen within the BE mucosa.
nihms435728f1.jpg
PMC3568520_02_nihms435728f1.jpg
F1
Mutation analysis of the TP53 gene showed a point mutation in exon 5 (H179N) in the ESCC and a deletion of 14 nucleotides in exon 6 (c.622_635delGACAGAAA CACTTT, p.D208SfsX3) in the HNSCC (Fig. 4D, Table 1), the latter being consistent with abrogated nonfunctional p53 protein.
Upper endoscopy showing a lesion suspected for a malignancy located in the distal esophagus (case B). The tumor was surrounded by Barrett's esophagus (BE). Areas of normal squamous epithelium were revealed distal to the tumor (in BE).
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F2
Upper endoscopy showed a nodular lesion in a BE segment (Fig. 2), which was histologically confirmed to be a poorly differentiated ESCC surrounded by areas of IM.
p63, CK5, CK7, and CDX2 immunohistochemistry photos (4x) of case A (A-D) and case B (E-F). p63 and CK5 are well-known, highly specific squamous cell carcinoma (SCC) markers. CDX2 is usually present during the neoplastic progression of Barrett's esophagus (BE) toward esophageal adenocarcinoma (EAC) and absent in normal squamous epithelium and SCCs. CK7 is found in the majority of EACs and in a subset (22-29%) of the esophageal SCCs (ESCCs).. CaseA: p63 (A) and CK5 (B) were strongly expressed in the ESCC, whereas staining was limited to absent in the adjacent BE mucosa. There was no expression of CK7 (C) and CDX2 (D) detected in the ESCC. In the BE glands, however, expression of both CK7 (C) and CDX2 (D) was revealed.. CaseB: p63 (E) and CK5 (F) were overwhelmingly present in the ESCC and undetectable in the surrounding BE glands. Expression of CK7 was found in both the ESCC and the BE mucosa. CDX2 was only revealed in the BE tissue.
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F3
As expected, CK7 and CDX2 were present in the BE tissue (Fig. 3A-D). CK7 was positive in the EC (Fig. 3E-G). CDX2 IHC was negative in the carcinoma and strongly positive in the adjacent BE mucosa (Fig. 3H). CK7 was also present in the BE glands (Fig. 3G), whereas p63 and CK5 were undetectable in BE (Fig. 3E-F).
p53 immunohistochemistry (a-c) and TP53 mutation analysis (D) results of case A. (A) The black arrows point out the esophageal squamous cell carcinoma (ESCC), and the white arrows show Barrett's esophagus (BE) glands. (B) p53 is strongly expressed in the ESCC arising in association with BE. (C) Absence of expression of p53 in the oral squamous cell carcinoma, indicating a null mutation. In the adjacent normal mucosa, weak staining of the basal cell layer is observed, as usually present, that serves as internal control for proper staining. (D) Deletion of 14 bp in exon 6 of the TP53 gene, which causes a change in frameshift reading and enables the reading of a stop codon 3 triplets after the first affected amino acid. This eventually results in a shorter, mutant and abrogated nonfunctional protein product.
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F4
Results of the p53 immunohistochemistry (IHC) are shown in Figure 4A-C. Mutation analysis of the TP53 gene showed a point mutation in exon 5 (H179N) in the ESCC and a deletion of 14 nucleotides in exon 6 (c.622_635delGACAGAAA CACTTT, p.D208SfsX3) in the HNSCC (Fig. 4D, Table 1), the latter being consistent with abrogated nonfunctional p53 protein.